Disease Information

General Information of the Disease (ID: DIS00071)

• Name: Gastric cancer
• ICD: ICD-11: 2B72

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 16 drug(s) in total

Capmatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.Y1230C (c.3689A>G)
• Resistant Drug: Capmatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NCI-H441 cells; Lung; Homo sapiens (Human); CVCL_1561
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: SNU638 cells; Ascites; Homo sapiens (Human); CVCL_0102
• In Vitro Model: NCI-H596 cells; Lung; Homo sapiens (Human); CVCL_1571
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vivo Model: Nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [2], [3], [4]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Inhibition; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Wnt/beta-catenin signaling pathway; Activation; hsa04310
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Balb/c athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: HOTAIR recruit the PRC2 complex to silence miR34a via H3k27me3 modification. HOTAIR knockdown inhibited DDP resistance of gastric cancer cells by upregulating miR-34a.

Key Molecule: hsa-mir-34 [2], [4]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Wnt/beta-catenin signaling pathway; Activation; hsa04310
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Balb/c athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: HOTAIR recruit the PRC2 complex to silence miR34a via H3k27me3 modification. HOTAIR knockdown inhibited DDP resistance of gastric cancer cells by upregulating miR-34a.

Key Molecule: hsa-mir-200c [5]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NER signaling pathway; Activation; hsa03420
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway.

Key Molecule: Small nucleolar RNA host gene 5 (SNHG5) [6]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Key Molecule: hsa_circ_0000199 [7]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: CircAkT3 regulates PIk3R1 expression, activates the PI3k/AkT signaling pathway and ultimately facilitates CDDP resistance by targeting miR-198 in vitro.

Key Molecule: hsa-miR-198 [7]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Dual-luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Circular RNA AkT3 upregulates PIk3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression.

Key Molecule: hsa-miR-633 [8]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-633 regulates chemotherapy resistance through downregulating FADD in gastric tumor cells.

Key Molecule: Long non-protein coding RNA (XLOC_006753) [9]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Activation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Long non-coding RNA XLOC_006753 promotes the development of multidrug resistance in gastric cancer cells through the PI3k/Akt/mTOR signaling pathway.

Key Molecule: Cancer susceptibility 2 (CASC2) [10]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by elevating miR-19a expression.

Key Molecule: hsa-mir-19a [10]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by elevating miR-19a expression.

Key Molecule: hsa-mir-30b [11]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA MALAT1 potentiates autophagy associated cisplatin resistance by suppressing the microRNA 30b/autophagy related gene 5 axis in gastric cancer.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [11]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA MALAT1 potentiates autophagy associated cisplatin resistance by suppressing the microRNA 30b/autophagy related gene 5 axis in gastric cancer.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [12]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR; Luciferase reporter assay; Pull down assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [12]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. MALAT1 regulates autophagy via ATG12.

Key Molecule: hsa-miR-23b-3p [12]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR; Luciferase reporter assay; Pull down assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. MALAT1 promotes autophagy-associated chemoresistance of GC cells via sequestration of miR23b-3p.

Key Molecule: hsa-mir-25 [13]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: microRNA-25 contributes to cisplatin resistance in gastric cancer cells by inhibiting forkhead box O3a.

Key Molecule: hsa-miR-148a-3p [14]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: BGC823CDDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901CDDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; PI/Annexin V-FITC Apoptosis Detection kit assay
• Mechanism Description: miR148a-3p reconstitution sensitized CDDP-resistant cells to CDDP treatment through promoting mitochondrial fission and decreasing AkAP1 expression level; miR148a-3p reconstitution in CDDP-resistant cells inhibits the cyto-protective autophagy by suppressing RAB12 expression and mTOR1 activation. miR148a-3p sensitization of GC cells to CDDP in vivo includes suppression of AkAP1 and RAB12 expression levels.

Key Molecule: H19, imprinted maternally expressed transcript (H19) [15]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FADD/Caspase 8/Caspase 3 signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis; Colony formation assay; Colony formation assay
• Mechanism Description: Long Noncoding RNA H19/miR675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 signaling Pathway. H19/miR675 targets FADD and inhibits caspase 8/caspase 3, H19 inhibits the expression of FADD through miR675 targeting.

Key Molecule: hsa-mir-675 [15]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FADD/Caspase 8/Caspase 3 signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis; Colony formation assay; Colony formation assay
• Mechanism Description: Long Noncoding RNA H19/miR675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 signaling Pathway. H19/miR675 targets FADD and inhibits caspase 8/caspase 3, H19 inhibits the expression of FADD through miR675 targeting.

Key Molecule: hsa-mir-145 [16]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: RT-PCR; qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer.

Key Molecule: hsa-mir-132 [17]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: ABCG2 signaling pathway; Activation; hsa02010
• Cell Pathway Regulation: SIRT1/CREB/ABCG2 signaling pathway; Regulation; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Upregulated miR132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway. The expression of miR132 was inversely correlated with SIRT1 in gastric cancer specimens. Down-regulation of SIRT1 led to a subsequent increase of the level of acetylated CREB which in turn activated the ABCG2 signaling pathway.

Key Molecule: hsa-mir-186 [18]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: SGC-7921 cells; Gastric; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The long noncoding RNA PVT1 functions as a competing endogenous RNA by sponging miR186 in gastric cancer.

Key Molecule: Pvt1 oncogene (PVT1) [18]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: SGC-7921 cells; Gastric; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The long noncoding RNA PVT1 functions as a competing endogenous RNA by sponging miR186 in gastric cancer.

Key Molecule: hsa-mir-491 [19]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: TUNEL assay; Clonogenic assay
• Mechanism Description: Inhibition of miR99a and miR491, or overexpress CAPNS1 can enhance cisplatin sensitivity of the resistant cells. miR99a and miR491 might be work as novel molecules regulate cisplatin resistance by directly targeting CAPNS1 associated pathway in human gastric cancer cells.

Key Molecule: hsa-mir-99a [19]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: TUNEL assay; Clonogenic assay
• Mechanism Description: Inhibition of miR99a and miR491, or overexpress CAPNS1 can enhance cisplatin sensitivity of the resistant cells. miR99a and miR491 might be work as novel molecules regulate cisplatin resistance by directly targeting CAPNS1 associated pathway in human gastric cancer cells.

Key Molecule: HOX transcript antisense RNA (HOTAIR) [20]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/MRP1 signaling pathway; Activation; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC-823/DDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric cell cycle assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR126 to activate the PI3k/AkT/MRP1 genes.

Key Molecule: hsa-mir-126 [20]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/MRP1 signaling pathway; Activation; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC-823/DDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qRT-PCR; Dual-luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric cell cycle assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR126 to activate the PI3k/AkT/MRP1 genes.

Key Molecule: hsa-miR-590-5p [21]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Activation; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay; Matrigel transwell assay
• Mechanism Description: miR590-5p regulates gastric cancer cell growth and chemosensitivity through RECk and the AkT/ERk pathway. RECk is a direct target of miR590-5p, knockdown of RECk accelerated cell proliferation and motility and decreased the drug sensitivity.The AkT/ERk and STAT3 signaling pathways were activated by miR590-5p overexpression.

Key Molecule: hsa-mir-27b [22]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/FU cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR27b.

Key Molecule: Urothelial cancer associated 1 (UCA1) [22]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/FU cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR27b.

Key Molecule: hsa-miR-613 [23]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Wound healing assay
• Mechanism Description: Elevated expression of miR-613 increased the sensitivity of GC cells to cisplatin and suppressed GC cell proliferation and migration by targeting SOX9.

Key Molecule: hsa-miR-876-3p [24]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: Si-TMED3 completely inhibited miR-876-3p inhibitor-stimulated enhancement in cisplatin resistance of cisplatin-resistant GC cells.

Key Molecule: hsa-miR-206 [25]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: MAPK2 signaling pathway; Regulation; hsa04011
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; EdU assay; Flow cytometry assay
• Mechanism Description: BGC823/DDP and SGC7901/DDP cell presented lower miR-206 than parental cells, plus higher MAPk3 mRNA or protein.

Key Molecule: hsa-miR-138-5p [26]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Low miR-138-5p levels and high ERCC1 and ERCC4 levels were associated with cisplatin resistance in gastric cancer cells.

Key Molecule: hsa-miR-193a-3p [27]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: Mitochondrial signaling pathway; Inhibition; hsa04217
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: SRSF2, a miR-193a-3p target gene, is downregulated and miR-193a-3p is upregulated, which induces the resistence to cisplatin.

Key Molecule: hsa-miR-135b-5p [28]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: SNU1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: SNU601 cells; Gastric; Homo sapiens (Human); CVCL_0101
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: ATP-Glo cell viability assay
• Mechanism Description: miR-135b-5p protects gastric cancer cells from cisplatin-induced apoptosis and miR-135b-5p overexpression or kLF4 down-regulation lead to cisplatin resistance in gastric cancer cells.

Key Molecule: hsa-mir-30a [29]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-sqPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The IC50 of CDDP in the SGC7901/CDDP-miR-30a mimics group was decreased to 8.56 M (P<0.001 vs. SGC7901/CDDP group), indicating increased chemosensitivity following miR-30a transfectionand the expression of P-gp protein was notably elevated in SGC7901/CDDP cells compared with SGC7901 cells.

Key Molecule: hsa-mir-34 [30]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The downregulation of miR-34a (+) the resistance of human GC cells to DDP treatment through regulation of cell proliferation and apoptosis via the regulation of the MET gene.

Key Molecule: hsa-mir-20a [31]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Flow cytometry assay; MTT assay
• Mechanism Description: miR-20a directly targeted CYLD, resulting in activation of the NFkB pathway and the downstream targets, livin and survivin, which potentially contributed to GC chemoresistance.

Key Molecule: hsa-mir-363 [32]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-363 promotes gastric cancer cells proliferation by inhibiting FBW7 expression and was associated with chemo-resistance of gastric cancer cells. Silencing FBW7 largely phenocopied miR-363-induced resistance to chemotherapy agents and promoted proliferation in gastric cancer cells. In addition, an inverse correlation between miR-363 and FBW7 mRNA expression was observed in gastric cancer tissues.

Key Molecule: hsa-miR-421 [33]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: N-Myc/ miR421 /ATM signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and induced cisplatin resistance in gastric cancer by targeting E-cadherin and caspase-3.

Key Molecule: hsa-mir-493 [34]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: miR493/DKK1 signaling pathway; Regulation; hsa05206
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Dkk1 expression was markedly decreased in GC tissues and serum samples. Dkk1 expression inversely correlated with miR-493 levels and is a direct target of miR-493. Moreover, miR-493 modulated the proliferation, invasion and chemo-sensitivity of GC cells via suppressing Dkk1 expression.

Key Molecule: Pvt1 oncogene (PVT1) [35]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: mTOR/HIF-1alpha /P-gp/MRP1 signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1alpha. Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [36]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Notch1 signaling pathway; Activation; hsa04330
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating LncRNA Ak022798 expression. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Furthermore, we used siRNA to interfere with LncRNA Ak022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased.

Key Molecule: hsa-mir-106a [37]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Activation; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-106a is up-regulated in the DDP-resistant SGC7901/DDP cells, Overexpression of miR-106a in the SGC7901 cells confers resistance to DDP, PTEN is a target gene of miR-106a, there was a consistent and strong inverse correlation between the miR-106a levels and PTEN, PTEN is a key signal molecule in miR-106a-regulated DDP resistance in SGC7901/DDP cells.

Key Molecule: hsa-mir-20a [38]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGR2 signaling pathway; Inhibition; hsa04625
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a.

Key Molecule: hsa-mir-19a [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: hsa-mir-19b [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: hsa-mir-21 [40]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell cycle; Inhibition; hsa04110
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: PTEN/PI3K/AKT signaling pathway; Activation; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The staining of PTEN was reversely correlated with miR-21 levels in tongue squamous cell carcinoma patients, PTEN is an important tumor suppressor gene and the functional inactivation of PTEN by regulation of its expression is relevant to many solid tumors. PETN involved in gastric cancer pathology and its down-regulation can lead to chemotherapeutic drug including cisplatin resistance in gastric cancer patients.

Key Molecule: hsa-mir-200b [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: hsa-mir-200c [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: hsa-miR-429 [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: HOX transcript antisense RNA (HOTAIR) [2], [3], [4]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Wnt/beta-catenin signaling pathway; Activation; hsa04310
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC-7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Balb/c athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: HOTAIR recruit the PRC2 complex to silence miR34a via H3K27me3 modification. HOTAIR knockdown inhibited DDP-resistance of gastric cancer cells by upregulating miR-34a.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [6]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [6]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [29]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The IC50 of CDDP in the SGC7901/CDDP-miR-30a mimics group was decreased to 8.56 M (P<0.001 vs. SGC7901/CDDP group), indicating increased chemosensitivity following miR-30a transfectionand the expression of P-gp protein was notably elevated in SGC7901/CDDP cells compared with SGC7901 cells.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [35]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: mTOR/HIF-1alpha /P-gp/MRP1 signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1alpha. Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [35]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: mTOR/HIF-1alpha /P-gp/MRP1 signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1alpha. Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-mir-21 [42]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: MFC cells; Gastric; Homo sapiens (Human); CVCL_5J48
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; FITC Annexin V Apoptosis Detection assay; Flow cytometric analysis
• Mechanism Description: Exosomal transfer of tumor-associated macrophages derived miR21 confer DDP resistance in gastric cancer Exosomal miR21 can be directly transferred from macrophages to the gastric cancer cells, where it suppresses cell apoptosis and enhances activation of PI3k/AkT signaling pathway by down-regulation of PTEN.

Key Molecule: Phosphatase and tensin homolog (PTEN) [42]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: MFC cells; Gastric; Homo sapiens (Human); CVCL_5J48
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; FITC Annexin V Apoptosis Detection assay; Flow cytometric analysis
• Mechanism Description: Exosomal transfer of tumor-associated macrophages derived miR21 confer DDP resistance in gastric cancer Exosomal miR21 can be directly transferred from macrophages to the gastric cancer cells, where it suppresses cell apoptosis and enhances activation of PI3k/AkT signaling pathway by down-regulation of PTEN.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [2], [3], [4]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Wnt/beta-catenin signaling pathway; Activation; hsa04310
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Balb/c athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RIP experiments assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3k/Akt and Wnt/beta-catenin signaling pathways by up-regulating miR34a.

Key Molecule: General transcription and DNA repair factor IIH helicase subunit XPB (ERCC3) [5]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NER signaling pathway; Activation; hsa03420
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway.

Key Molecule: DNA repair endonuclease XPF (ERCC4) [5]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NER signaling pathway; Activation; hsa03420
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [6]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Key Molecule: Apoptosis regulator BAX (BAX) [6]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Key Molecule: PI3-kinase regulatory subunit alpha (PIK3R1) [7]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: CircAkT3 regulates PIk3R1 expression, activates the PI3k/AkT signaling pathway and ultimately facilitates CDDP resistance by targeting miR-198 in vitro.

Key Molecule: FAS-associated death domain protein (FADD) [8]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-633 regulates chemotherapy resistance through downregulating FADD in gastric tumor cells.

Key Molecule: Autophagy protein 5 (ATG5) [11]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA MALAT1 potentiates autophagy associated cisplatin resistance by suppressing the microRNA 30b/autophagy related gene 5 axis in gastric cancer.

Key Molecule: Ubiquitin-like protein ATG12 (ATG12) [12]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. MALAT1 regulates autophagy via ATG12.

Key Molecule: Forkhead box protein O3 (FOXO3) [13]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: microRNA-25 contributes to cisplatin resistance in gastric cancer cells by inhibiting forkhead box O3a.

Key Molecule: A-kinase anchor protein 1 (AKAP1) [14]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: BGC823CDDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901CDDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; PI/Annexin V-FITC Apoptosis Detection kit assay
• Mechanism Description: miR148a-3p reconstitution sensitized CDDP-resistant cells to CDDP treatment through promoting mitochondrial fission and decreasing AkAP1 expression level; miR148a-3p reconstitution in CDDP-resistant cells inhibits the cyto-protective autophagy by suppressing RAB12 expression and mTOR1 activation. miR148a-3p sensitization of GC cells to CDDP in vivo includes suppression of AkAP1 and RAB12 expression levels.

Key Molecule: Ras-related protein Rab-12 (RAB12) [14]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: BGC823CDDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901CDDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; PI/Annexin V-FITC Apoptosis Detection kit assay
• Mechanism Description: miR148a-3p reconstitution sensitized CDDP-resistant cells to CDDP treatment through promoting mitochondrial fission and decreasing AkAP1 expression level; miR148a-3p reconstitution in CDDP-resistant cells inhibits the cyto-protective autophagy by suppressing RAB12 expression and mTOR1 activation. miR148a-3p sensitization of GC cells to CDDP in vivo includes suppression of AkAP1 and RAB12 expression levels.

Key Molecule: FAS-associated death domain protein (FADD) [15]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FADD/Caspase 8/Caspase 3 signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis; Colony formation assay; Colony formation assay
• Mechanism Description: Long Noncoding RNA H19/miR675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 signaling Pathway. FADD, a significant gene regulating cell apoptosis, is a direct target of miR675. H19/miR675 targets FADD and inhibits caspase 8/caspase 3, H19 inhibits the expression of FADD through miR675 targeting.

Key Molecule: Extracellular matrix receptor III (CD44) [16]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer.

Key Molecule: Hypoxia-inducible factor 1-alpha (HIF1A) [18]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: SGC-7921 cells; Gastric; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: PVT1 knockdown suppressed the HIF-1alpha mRNA and protein expression levels of HIF-1alpha in BGC-823 cells, PVT1 promoted the HIF-1alpha expression by regulating miR186.

Key Molecule: Calpain small subunit 1 (CAPNS1) [19]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: TUNEL assay; Clonogenic assay
• Mechanism Description: Inhibition of miR99a and miR491, or overexpress CAPNS1 can enhance cisplatin sensitivity of the resistant cells. miR99a and miR491 might be work as novel molecules regulate cisplatin resistance by directly targeting CAPNS1 associated pathway in human gastric cancer cells.

Key Molecule: PI3-kinase regulatory subunit beta (PIK3R2) [20]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/MRP1 signaling pathway; Activation; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC-823/DDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric cell cycle assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: HOTAIR was shown to directly bind to and inhibit miR126 expression and then to promote VEGFA and PIk3R2 expression and activate the PI3k/AkT/MRP1 pathway.

Key Molecule: Vascular endothelial growth factor A (VEGFA) [20]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/MRP0 signaling pathway; Activation; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC-823/DDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric cell cycle assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: HOTAIR was shown to directly bind to and inhibit miR126 expression and then to promote VEGFA and PIk3R2 expression and activate the PI3k/AkT/MRP1 pathway.

Key Molecule: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) [21]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Activation; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Matrigel transwell assay
• Mechanism Description: miR590-5p regulates gastric cancer cell growth and chemosensitivity through RECk and the AkT/ERk pathway. RECk is a direct target of miR590-5p, knockdown of RECk accelerated cell proliferation and motility and decreased the drug sensitivity.The AkT/ERk and STAT3 signaling pathways were activated by miR590-5p overexpression.

Key Molecule: Transcription factor SOX-9 (SOX9) [23]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Wound healing assay
• Mechanism Description: Elevated expression of miR-613 increased the sensitivity of GC cells to cisplatin and suppressed GC cell proliferation and migration by targeting SOX9.

Key Molecule: Transmembrane emp24 domain-containing protein 3 (TMED3) [24]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: Si-TMED3 completely inhibited miR-876-3p inhibitor-stimulated enhancement in cisplatin resistance of cisplatin-resistant GC cells.

Key Molecule: Mitogen-activated protein kinase 3 (MAPK3) [25]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: MAPK2 signaling pathway; Regulation; hsa04011
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; EdU assay; Flow cytometry assay
• Mechanism Description: BGC823/DDP and SGC7901/DDP cell presented lower miR-206 than parental cells, plus higher MAPk3 mRNA or protein.

Key Molecule: DNA excision repair protein ERCC-1 (ERCC1) [26]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Low miR-138-5p levels and high ERCC1 and ERCC4 levels were associated with cisplatin resistance in gastric cancer cells.

Key Molecule: DNA repair endonuclease XPF (ERCC4) [26]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Low miR-138-5p levels and high ERCC1 and ERCC4 levels were associated with cisplatin resistance in gastric cancer cells.

Key Molecule: Serine/arginine-rich splicing factor 2 (SRSF2) [27]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: Mitochondrial signaling pathway; Inhibition; hsa04217
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: SRSF2, a miR-193a-3p target gene, is downregulated and miR-193a-3p is upregulated, which induces the resistence to cisplatin.

Key Molecule: Krueppel-like factor 4 (KLF4) [28]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: SNU1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: SNU601 cells; Gastric; Homo sapiens (Human); CVCL_0101
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: ATP-Glo cell viability assay
• Mechanism Description: miR-135b-5p protects gastric cancer cells from cisplatin-induced apoptosis and miR-135b-5p overexpression or kLF4 down-regulation lead to cisplatin resistance in gastric cancer cells.

Key Molecule: Hepatocyte growth factor receptor (MET) [30]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The downregulation of miR-34a (+) the resistance of human GC cells to DDP treatment through regulation of cell proliferation and apoptosis via the regulation of the MET gene.

Key Molecule: Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) [31]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis; Immunohistochemistry assay
• Experiment for Drug Resistance: Flow cytometry assay; MTT assay
• Mechanism Description: miR-20a directly targeted CYLD, resulting in activation of the NFkB pathway and the downstream targets, livin and survivin, which potentially contributed to GC chemoresistance.

Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7) [32]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-363 promotes gastric cancer cells proliferation by inhibiting FBW7 expression and was associated with chemo-resistance of gastric cancer cells. Silencing FBW7 largely phenocopied miR-363-induced resistance to chemotherapy agents and promoted proliferation in gastric cancer cells. In addition, an inverse correlation between miR-363 and FBW7 mRNA expression was observed in gastric cancer tissues.

Key Molecule: Caspase-3 (CASP3) [33]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: N-Myc/ miR421 /ATM signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• Experiment for Molecule Alteration: Western blot analysis; Flow cytometric assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and induced cisplatin resistance in gastric cancer by targeting E-cadherin and caspase-3.

Key Molecule: Cadherin-1 (CDH1) [33]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: N-Myc/ miR421 /ATM signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• Experiment for Molecule Alteration: Western blot analysis; Flow cytometric assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and induced cisplatin resistance in gastric cancer by targeting E-cadherin and caspase-3.

Key Molecule: Dickkopf-related protein 1 (DKK1) [34]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: miR493/DKK1 signaling pathway; Regulation; hsa05206
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Dkk1 expression was markedly decreased in GC tissues and serum samples. Dkk1 expression inversely correlated with miR-493 levels and is a direct target of miR-493. Moreover, miR-493 modulated the proliferation, invasion and chemo-sensitivity of GC cells via suppressing Dkk1 expression.

Key Molecule: Hypoxia-inducible factor 1-alpha (HIF1A) [35]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: mTOR/HIF-1alpha /P-gp/MRP1 signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1alpha. Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [35]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: mTOR/HIF-1alpha /P-gp/MRP1 signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1alpha. Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Key Molecule: Caspase-3 (CASP3) [36]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Notch1 signaling pathway; Activation; hsa04330
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating LncRNA Ak022798 expression. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Furthermore, we used siRNA to interfere with LncRNA Ak022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased.

Key Molecule: Caspase-8 (CASP8) [36]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Notch1 signaling pathway; Activation; hsa04330
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating LncRNA Ak022798 expression. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Furthermore, we used siRNA to interfere with LncRNA Ak022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased.

Key Molecule: Phosphatase and tensin homolog (PTEN) [37], [39], [40]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Activation; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-106a is up-regulated in the DDP-resistant SGC7901/DDP cells, Overexpression of miR-106a in the SGC7901 cells confers resistance to DDP, PTEN is a target gene of miR-106a, there was a consistent and strong inverse correlation between the miR-106a levels and PTEN, PTEN is a key signal molecule in miR-106a-regulated DDP resistance in SGC7901/DDP cells.

Key Molecule: E3 SUMO-protein ligase EGR2 (EGR2) [38]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGR2 signaling pathway; Inhibition; hsa04625
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: Sphingosine-1-phosphate lyase 1 (SGPL1) [43]

• Resistant Disease: Gastric cardia adenocarcinoma [ICD-11: 2B72.2]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: S1P could lead to cytotoxic drug resistance in gastroesophegal cancer acting in an autocrine or paracrine manner via cell surface S1P receptors following transportation out of the cytosol. Alternatively S1P may mediate cytotoxic drug resistance acting intracellularly by counteracting apoptosis mediated by its pro-apoptotic precursor ceramide or interaction with known intracellular targets involved in cancer pathogenesis and cytotoxic drug resistance such as Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC 2) to which S1P directly binds and inhibits, and TNF Receptor-Associated Factor 2 (TRAF 2), or Protein Kinase C (PKC). S1P production controlled by SPHK1 and SGPL1 are key determinants of cytotoxic drug resistance and that decreasing S1P production in cancer cells could lead to increased cytotoxic sensitivity.

Key Molecule: Sphingosine kinase 1 (SPHK1) [43]

• Resistant Disease: Gastric cardia adenocarcinoma [ICD-11: 2B72.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: S1P could lead to cytotoxic drug resistance in gastroesophegal cancer acting in an autocrine or paracrine manner via cell surface S1P receptors following transportation out of the cytosol. Alternatively S1P may mediate cytotoxic drug resistance acting intracellularly by counteracting apoptosis mediated by its pro-apoptotic precursor ceramide or interaction with known intracellular targets involved in cancer pathogenesis and cytotoxic drug resistance such as Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC 2) to which S1P directly binds and inhibits, and TNF Receptor-Associated Factor 2 (TRAF 2), or Protein Kinase C (PKC). S1P production controlled by SPHK1 and SGPL1 are key determinants of cytotoxic drug resistance and that decreasing S1P production in cancer cells could lead to increased cytotoxic sensitivity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-574-3p [44]

• Sensitive Disease: Gastric carcinoma [ICD-11: 2B72.Z]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-574-3p regulates epithelial mesenchymal transition and cisplatin resistance via targeting ZEB1 in human gastric carcinoma cells.

Key Molecule: hsa-mir-320 [45]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Overexpression of miR320a inhibited tumor growth in vitro and in vivo and increased the sensitivity of GC cells to cisplatin by targeting ADAM10.

Key Molecule: HOX transcript antisense RNA (HOTAIR) [4]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Caspase-3 activity detection; MTT assay
• Mechanism Description: Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3k/Akt and Wnt/beta-catenin signaling pathways by up-regulating miR34a.

Key Molecule: hsa-mir-34 [4]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual-luciferase report assay; RNA immunoprecipitation (RIP) assay; qRT-PCR
• Experiment for Drug Resistance: Caspase-3 activity detection; MTT assay
• Mechanism Description: Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3k/Akt and Wnt/beta-catenin signaling pathways by up-regulating miR34a.

Key Molecule: hsa-mir-101 [46]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: p38/MAPK/AKT signaling pathway; Regulation; hsa04010
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR101 alleviates chemoresistance of gastric cancer cells by targeting ANXA2, ectopic expression of ANXA2 reversed the effect of miR101 on P-gp expression, cell viability and apoptosis. knockdown of ANXA2 increased sensitivity to doxorubicin, 5-FU and DDP by regulating p38MAPk and AkT pathways.

Key Molecule: hsa-mir-200c [47]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BIRC6/p53-mediated apoptosis signaling pathway; Activation; hsa04210
• Cell Pathway Regulation: ZEB2 signaling pathway; Inhibition; hsa05202
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-200c regulates cisplatin resistance by targeting ZEB2 in human gastric cancer cells.

Key Molecule: hsa-miR-33b-5p [48]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric apoptosis assay
• Mechanism Description: miR33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting HMGA2 expression.

Key Molecule: NAD-dependent protein deacetylase sirtuin-1 (SIRT1) [17]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: SIRT1/CREB/ABCG2 signaling pathway; Regulation; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Upregulated miR132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway. Overexpression of SIRT1 down-regulated ABCG2 expression by promoting the de-acetylation of the transcription factor CREB. CREB was further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription.

Key Molecule: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [49]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: Silencing LncRNA HULC could enhance chemotherapy induced apoptosis in GC cells.

Key Molecule: hsa-mir-129 [50]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Intrinsic apoptotic signaling pathway; Activation; hsa04210
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR129 reversed cisplatin-resistance through inhibiting the P-gp expression in GC cells. miR129 activated the intrinsic apoptotic pathway via upregulating caspase-9 and caspase-3.

Key Molecule: hsa-miR-524-5p [51]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: AZ521 cells; Gastric; Homo sapiens (Human); CVCL_2862
• In Vitro Model: SC-M1 cells; Gastric; Homo sapiens (Human); CVCL_G299
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Transwell cell migration assay
• Mechanism Description: Upregulation of microRNA-524-5p enhances the cisplatin sensitivity of gastric cancer cells by modulating proliferation and metastasis via targeting SOX9, SOX9 overexpression could counteracts the chemosensitizing effects of miR524-5p.

Key Molecule: hsa-mir-874 [52]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR 874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1.

Key Molecule: hsa-mir-495 [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Key Molecule: hsa-miR-17-5p [54]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Down-regulation of miR-17-5p reverses drug resistance of gastric cancer cells and increases p21 expression in SGC7901/DDP cells.

Key Molecule: hsa-mir-149 [55]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-149 enhances SGC7901/DDP cell sensitivity to cisplatin by downregulating FoxM1 expression.

Key Molecule: hsa-mir-125b [56]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overexpression of miR-125b improved the chemosensitivity of DDP in HGC-27 and MGC-803 cells and miR-125b obviously inhibited the expression of HER2 at protein level in HGC-27 and MGC-803 cells.

Key Molecule: hsa-mir-30a [57]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR; Western blot analysiss
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: EMT is associated with cisplatin resistance in gastric cancer. miR-30a is an important miRNA modulating EMT and cisplatin sensitivity of SGC-7901 and SGC-7901/DDP cells.

Key Molecule: hsa-mir-181a [58]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901/CDDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: miR-181a inhibited autophagy in cisplatin-resistant cell line SGC7901/CDDP. ATG5 was a potential target of miR-181a. miR-181a sensitized SGC7901/CDDP cells to cisplatin in vivo and in vitro.

Key Molecule: hsa-mir-101 [59]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry analysis assay
• Mechanism Description: miR-101 inhibits proliferation and promotes DDP-induced apoptosis of SGC7901/DDP cells via negatively mediating the expression of VEGF-C, which facilitate gastric cancer cells sensitivity to Cisplatin.

Key Molecule: hsa-mir-29b [60]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The expression of miR-29b was significantly upregualted by cisplatin treatment,while its target gene AkT2 was downregulated. The up-regulation of miR-29b (+) the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29b (+) the cisplatin resistance. Rescue experiments demonstrated that the miR-29b might regulate cisplatin resistance of gastric cancer cell by targeting PI3k/Akt pathway. The expressions of the other two members of miR-29 family, miR-29a/c, were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell's resistance to cisplatin.

Key Molecule: hsa-mir-26a [61]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: NRAS and E2F2 as the direct targets of miR-26a were further confirmed in luciferase activity assays and miR-26a-mediated these two genes expression analysis. Our results also found that knockdown of NRAS or E2F2 sensitize GC cells to cisplatin. miR-26a overexpression has been demonstrated to improve the sensitivity of GC cells to cisplatin and this effect was considered to be mediated via its targets NRAS and E2F2.

Key Molecule: hsa-miR-23b-3p [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: SCID-SHO mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: Long non-protein coding RNA (AK022798) [36]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Notch1 signaling pathway; Inhibition; hsa04330
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating LncRNA Ak022798 expression. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Furthermore, we used siRNA to interfere with LncRNA Ak022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased.

Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [36]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Notch1 signaling pathway; Inhibition; hsa04330
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating LncRNA Ak022798 expression. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Furthermore, we used siRNA to interfere with LncRNA Ak022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased.

Key Molecule: hsa-mir-218 [63]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: WST-1 kit assay
• Mechanism Description: miR-218 increased chemosensitivity of gastric cancer cells to cisplatin via its target mTOR inhibitor.

Key Molecule: hsa-mir-503 [64]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R signaling pathway; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Clonogenic assay
• Mechanism Description: miR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines. Additionally, downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line. An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503. Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins, inhibited proliferation, and sensitized the cells to DDP-induced apoptosis.

Key Molecule: hsa-mir-1271 [65]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R/IRS1 signaling pathway; Regulation; hsa04212
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Enforced miR-1271 expression repressed the protein levels of its targets, inhibited proliferation of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Overall, on the basis of the results of our study, we proposed that miR-1271 could regulate cisplatin resistance in human gastric cancer cells, at least partially, via targeting the IGF1R/IRS1 pathway.

Key Molecule: hsa-mir-185 [66]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Trypan blue exclusion assay; Tunel assay
• Mechanism Description: Restoration of miR-185 alone can inhibit gastric cancer tumor growth. Moreover, combination therapy using enforced miR-185 expression and lower dose chemotherapeutic drugs had an effective therapeutic activity against large established tumors, with decreased host toxicity. miR-185 increases the chemosensitivity of gastric cancer cells in vitro and in vivo. It exerts tumor-suppressing function through negatively regulating ARC. Besides, miR-185 upregulation in response to cisplatin or doxorubicin treatment in gastric cancer cells is dependent on RUNX3 transcriptional activity.

Key Molecule: hsa-mir-141 [67]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Knockdown miR-141 expression in 7901/DDP and 7901 cells could significantly improve cisplatin sensitivity. Over-expression of miR-141 resulted in (+) resistance to cisplatin in both gastric cancer cells. We also demonstrated that miR-141 directly targets kEAP1 by luciferase reporter assay, and that down-regulation of kEAP1 induces cisplatin resistance. Conversely, over-expression of kEAP1 significantly (+) cisplatin sensitivity. Our 75 pairs of tissues also showed that kEAP1 was significantly up-regulated in H. pylori-positive tissues.

Key Molecule: hsa-mir-34 [68]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT/survivin signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-34aexpression was down-regulated in cisplatin-resistant cell lines.miR-34a over-expression could improve the sensitivity ofgastric cancer cells against cisplatin-based chemotherapies,with PI3k/AkT/survivin signaling pathway possibly involvedin the mechanism.

Key Molecule: hsa-miR-508-5p [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: hsa-mir-200c [70]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The knockdown of RhoE enhanced the sensitivity of SGC7901/DDP cells and changed expres-sion of some genes. Transfection of pre-miR-200c reduces RhoEexpression. miRNA-200cregulated the sensitivity of chemotherapy to cisplatin(DDP) in gastric cancer by possibly targeting RhoE.

Key Molecule: hsa-mir-497 [71]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Enforced miR-497 expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, has-miR-497 could play a role in both gastric and lung cancer cell lines at least in part by modulation of apoptosis via targeting BCL2.

Key Molecule: hsa-mir-181 [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: hsa-mir-34 [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: hsa-mir-15b [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Key Molecule: hsa-mir-16 [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [17]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: SIRT1/CREB/ABCG2 signaling pathway; Regulation; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Upregulated miR132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway. Overexpression of SIRT1 down-regulated ABCG2 expression by promoting the de-acetylation of the transcription factor CREB. CREB was further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [50]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Intrinsic apoptotic signaling pathway; Activation; hsa04210
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR129 reversed cisplatin-resistance through inhibiting the P-gp expression in GC cells. miR129 activated the intrinsic apoptotic pathway via upregulating caspase-9 and caspase-3.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-mir-30a [75]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR30a can decrease multidrug resistance (MDR) of gastric cancer cells, miR30a overexpression decreased the expression of P-gp, a MDR-related protein. It is also an important miRNA modulating EMT of the cancer cells.

Key Molecule: Death effector domain-containing protein (DEDD) [76]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, impairing EMT in GC cells.

Key Molecule: hsa-mir-17 [76]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, impairing EMT in GC cells.

Key Molecule: Catenin beta-1 (CTNNB1) [77]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Silencing of ZFAS1 augmented the sensitivity to cis-platinum or paclitaxel in gastric cancer cancer cells and silencing of ZFAS1-induced inhibition of malignancies was reversed by beta-catenin.

Key Molecule: ZNFX1 antisense RNA 1 (ZFAS1) [77]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Silencing of ZFAS1 augmented the sensitivity to cis-platinum or paclitaxel in gastric cancer cancer cells and silencing of ZFAS1-induced inhibition of malignancies was reversed by beta-catenin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [44]

• Sensitive Disease: Gastric carcinoma [ICD-11: 2B72.Z]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-574-3p regulates epithelial mesenchymal transition and cisplatin resistance via targeting ZEB1 in human gastric carcinoma cells.

Key Molecule: Mammalian disintegrin-metalloprotease (ADAM10) [45]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter activity assay
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Overexpression of miR320a inhibited tumor growth in vitro and in vivo and increased the sensitivity of GC cells to cisplatin by targeting ADAM10.

Key Molecule: Annexin A2 (ANXA2) [46]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: p38/MAPK/AKT signaling pathway; Regulation; hsa04010
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RIP assay; Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR101 alleviates chemoresistance of gastric cancer cells by targeting ANXA2, ectopic expression of ANXA2 reversed the effect of miR101 on P-gp expression, cell viability and apoptosis. knockdown of ANXA2 increased sensitivity to doxorubicin, 5-FU and DDP by regulating p38MAPk and AkT pathways.

Key Molecule: Zinc finger E-box-binding homeobox 2 (ZEB2) [47]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ZEB2 signaling pathway; Inhibition; hsa05202
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Dual luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-200c regulates cisplatin resistance by targeting ZEB2 in human gastric cancer cells.

Key Molecule: High mobility group protein HMGI-C (HMGA2) [48]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric apoptosis assay
• Mechanism Description: miR33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting HMGA2 expression.

Key Molecule: Transcription factor SOX-9 (SOX9) [51]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: AZ521 cells; Gastric; Homo sapiens (Human); CVCL_2862
• In Vitro Model: SC-M1 cells; Gastric; Homo sapiens (Human); CVCL_G299
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Transwell cell migration assay
• Mechanism Description: Upregulation of microRNA-524-5p enhances the cisplatin sensitivity of gastric cancer cells by modulating proliferation and metastasis via targeting SOX9, SOX9 overexpression could counteracts the chemosensitizing effects of miR524-5p.

Key Molecule: Autophagy-related protein 16-1 (ATG16L1) [52]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR 874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Key Molecule: Ribonuclease P protein subunit p21 (RPP21) [54]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Down-regulation of miR-17-5p reverses drug resistance of gastric cancer cells and increases p21 expression in SGC7901/DDP cells.

Key Molecule: Forkhead box protein M1 (FOXM1) [55]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-149 enhances SGC7901/DDP cell sensitivity to cisplatin by downregulating FoxM1 expression.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [56]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overexpression of miR-125b improved the chemosensitivity of DDP in HGC-27 and MGC-803 cells and miR-125b obviously inhibited the expression of HER2 at protein level in HGC-27 and MGC-803 cells.

Key Molecule: Insulin-like growth factor 1 receptor (IGF1R) [65], [64]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R signaling pathway; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R/IRS1 signaling pathway; Regulation; hsa04212
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Clonogenic assay
• Mechanism Description: Enforced miR-1271 expression repressed the protein levels of its targets, inhibited proliferation of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Overall, on the basis of the results of our study, we proposed that miR-1271 could regulate cisplatin resistance in human gastric cancer cells, at least partially, via targeting the IGF1R/IRS1 pathway. and miR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines. Additionally, downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line. An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503. Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins, inhibited proliferation, and sensitized the cells to DDP-induced apoptosis.

Key Molecule: Autophagy protein 5 (ATG5) [58]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901/CDDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: miR-181a inhibited autophagy in cisplatin-resistant cell line SGC7901/CDDP. ATG5 was a potential target of miR-181a. miR-181a sensitized SGC7901/CDDP cells to cisplatin in vivo and in vitro.

Key Molecule: Vascular endothelial growth factor C (VEGFC) [59]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry analysis assay
• Mechanism Description: miR-101 inhibits proliferation and promotes DDP-induced apoptosis of SGC7901/DDP cells via negatively mediating the expression of VEGF-C, which facilitate gastric cancer cells sensitivity to Cisplatin.

Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [60]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The expression of miR-29b was significantly upregualted by cisplatin treatment,while its target gene AkT2 was downregulated. The up-regulation of miR-29b (+) the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29b (+) the cisplatin resistance. Rescue experiments demonstrated that the miR-29b might regulate cisplatin resistance of gastric cancer cell by targeting PI3k/Akt pathway. The expressions of the other two members of miR-29 family, miR-29a/c, were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell's resistance to cisplatin.

Key Molecule: Transcription factor E2F2 (E2F2) [61]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: NRAS and E2F2 as the direct targets of miR-26a were further confirmed in luciferase activity assays and miR-26a-mediated these two genes expression analysis. Our results also found that knockdown of NRAS or E2F2 sensitize GC cells to cisplatin. miR-26a overexpression has been demonstrated to improve the sensitivity of GC cells to cisplatin and this effect was considered to be mediated via its targets NRAS and E2F2.

Key Molecule: GTPase Nras (NRAS) [61]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: NRAS and E2F2 as the direct targets of miR-26a were further confirmed in luciferase activity assays and miR-26a-mediated these two genes expression analysis. Our results also found that knockdown of NRAS or E2F2 sensitize GC cells to cisplatin. miR-26a overexpression has been demonstrated to improve the sensitivity of GC cells to cisplatin and this effect was considered to be mediated via its targets NRAS and E2F2.

Key Molecule: Ubiquitin-like protein ATG12 (ATG12) [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: High mobility group protein B2 (HMGB2) [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [63]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Regulation; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Expression
• Experiment for Drug Resistance: WST-1 kit assay
• Mechanism Description: miR-218 increased chemosensitivity of gastric cancer cells to cisplatin via its target mTOR inhibitor.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [65]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R/IRS1 signaling pathway; Regulation; hsa04212
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Transwell assay
• Mechanism Description: Enforced miR-1271 expression repressed the protein levels of its targets, inhibited proliferation of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Overall, on the basis of the results of our study, we proposed that miR-1271 could regulate cisplatin resistance in human gastric cancer cells, at least partially, via targeting the IGF1R/IRS1 pathway.

Key Molecule: Insulin receptor substrate 1 (IRS1) [65]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R/IRS1 signaling pathway; Regulation; hsa04212
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Wound Healing assay; Matrigel transmembrane invasion assay
• Mechanism Description: Enforced miR-1271 expression repressed the protein levels of its targets, inhibited proliferation of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Overall, on the basis of the results of our study, we proposed that miR-1271 could regulate cisplatin resistance in human gastric cancer cells, at least partially, via targeting the IGF1R/IRS1 pathway.

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [65]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: IGF1R/IRS1 signaling pathway; Regulation; hsa04212
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Transwell assay
• Mechanism Description: Enforced miR-1271 expression repressed the protein levels of its targets, inhibited proliferation of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Overall, on the basis of the results of our study, we proposed that miR-1271 could regulate cisplatin resistance in human gastric cancer cells, at least partially, via targeting the IGF1R/IRS1 pathway.

Key Molecule: Activity-regulated cytoskeleton-associated protein (ARC) [66]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Trypan blue exclusion assay; Tunel assay
• Mechanism Description: Restoration of miR-185 alone can inhibit gastric cancer tumor growth. Moreover, combination therapy using enforced miR-185 expression and lower dose chemotherapeutic drugs had an effective therapeutic activity against large established tumors, with decreased host toxicity. miR-185 increases the chemosensitivity of gastric cancer cells in vitro and in vivo. It exerts tumor-suppressing function through negatively regulating ARC. Besides, miR-185 upregulation in response to cisplatin or doxorubicin treatment in gastric cancer cells is dependent on RUNX3 transcriptional activity.

Key Molecule: Kelch-like ECH-associated protein 1 (KEAP1) [67]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Knockdown miR-141 expression in 7901/DDP and 7901 cells could significantly improve cisplatin sensitivity. Over-expression of miR-141 resulted in (+) resistance to cisplatin in both gastric cancer cells. We also demonstrated that miR-141 directly targets kEAP1 by luciferase reporter assay, and that down-regulation of kEAP1 induces cisplatin resistance. Conversely, over-expression of kEAP1 significantly (+) cisplatin sensitivity. Our 75 pairs of tissues also showed that kEAP1 was significantly up-regulated in H. pylori-positive tissues.

Key Molecule: DNA-directed RNA polymerase I subunit RPA12 (RPA12) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: Rho-related GTP-binding protein RhoE (RND3) [70]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The knockdown of RhoE enhanced the sensitivity of SGC7901/DDP cells and changed expres-sion of some genes. Transfection of pre-miR-200c reduces RhoEexpression. miRNA-200cregulated the sensitivity of chemotherapy to cisplatin(DDP) in gastric cancer by possibly targeting RhoE.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: High mobility group protein HMGI-C (HMGA2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: Neurogenic locus notch homolog protein (NOTCH) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-363 [32]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-363 promotes gastric cancer cells proliferation by inhibiting FBW7 expression and was associated with chemo-resistance of gastric cancer cells. Silencing FBW7 largely phenocopied miR-363-induced resistance to chemotherapy agents and promoted proliferation in gastric cancer cells. In addition, an inverse correlation between miR-363 and FBW7 mRNA expression was observed in gastric cancer tissues.

Key Molecule: hsa-mir-20a [38]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGR2 signaling pathway; Inhibition; hsa04625
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7) [32]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-363 promotes gastric cancer cells proliferation by inhibiting FBW7 expression and was associated with chemo-resistance of gastric cancer cells. Silencing FBW7 largely phenocopied miR-363-induced resistance to chemotherapy agents and promoted proliferation in gastric cancer cells. In addition, an inverse correlation between miR-363 and FBW7 mRNA expression was observed in gastric cancer tissues.

Key Molecule: E3 SUMO-protein ligase EGR2 (EGR2) [38]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGR2 signaling pathway; Inhibition; hsa04625
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-20a promoted the growth, migration and invasion of GC cells, enhanced the chemoresistance of GC cells to cisplatin and docetaxel. Luciferase activity and Western blot confirmed that miR-20a negatively regulated EGR2 expression. Overexpression of EGR2 significantly attenuated the oncogenic effect of miR-20a.

Key Molecule: Hypoxia-inducible factor 2-alpha (EPAS1) [78]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Over-expression of EPAS-1 increased the expression of PXR responsive genes, enhanced the proliferation of BGC-823 cells and boosted the resistance of BGC-823 cells against the cytotoxicity of chemotherapeutic drugs, e.g. Mitomycin C and Paclitaxel.EPAS-1 reduces BGC-823 cell apoptosis induced by Mitomycin C and Paclitaxel.

Key Molecule: Sphingosine-1-phosphate lyase 1 (SGPL1) [43]

• Resistant Disease: Gastric cardia adenocarcinoma [ICD-11: 2B72.2]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: S1P could lead to cytotoxic drug resistance in gastroesophegal cancer acting in an autocrine or paracrine manner via cell surface S1P receptors following transportation out of the cytosol. Alternatively S1P may mediate cytotoxic drug resistance acting intracellularly by counteracting apoptosis mediated by its pro-apoptotic precursor ceramide or interaction with known intracellular targets involved in cancer pathogenesis and cytotoxic drug resistance such as Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC 2) to which S1P directly binds and inhibits, and TNF Receptor-Associated Factor 2 (TRAF 2), or Protein Kinase C (PKC). S1P production controlled by SPHK1 and SGPL1 are key determinants of cytotoxic drug resistance and that decreasing S1P production in cancer cells could lead to increased cytotoxic sensitivity.

Key Molecule: Sphingosine kinase 1 (SPHK1) [43]

• Resistant Disease: Gastric cardia adenocarcinoma [ICD-11: 2B72.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: S1P could lead to cytotoxic drug resistance in gastroesophegal cancer acting in an autocrine or paracrine manner via cell surface S1P receptors following transportation out of the cytosol. Alternatively S1P may mediate cytotoxic drug resistance acting intracellularly by counteracting apoptosis mediated by its pro-apoptotic precursor ceramide or interaction with known intracellular targets involved in cancer pathogenesis and cytotoxic drug resistance such as Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC 2) to which S1P directly binds and inhibits, and TNF Receptor-Associated Factor 2 (TRAF 2), or Protein Kinase C (PKC). S1P production controlled by SPHK1 and SGPL1 are key determinants of cytotoxic drug resistance and that decreasing S1P production in cancer cells could lead to increased cytotoxic sensitivity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-33b-5p [48]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric apoptosis assay
• Mechanism Description: miR33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting HMGA2 expression.

Key Molecule: hsa-mir-34 [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: High mobility group protein HMGI-C (HMGA2) [48]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric apoptosis assay
• Mechanism Description: miR33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting HMGA2 expression.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: High mobility group protein HMGI-C (HMGA2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: Neurogenic locus notch homolog protein (NOTCH) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-1 [79]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells.

Key Molecule: hsa-miR-633 [8]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-633 regulates chemotherapy resistance through downregulating FADD in gastric tumor cells.

Key Molecule: hsa-mir-27b [22]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/FU cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR27b.

Key Molecule: Urothelial cancer associated 1 (UCA1) [22]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/FU cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR27b.

Key Molecule: hsa-mir-494 [80]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: microRNA 494 increases chemosensitivity to doxorubicin in gastric cancer cells by targeting phosphodiesterases 4D.

Key Molecule: hsa-mir-20a [81]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: MAPK/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The restoration of miR-20a expression significantly reduced LRIG1-induced GC cell chemosensitivity.

Key Molecule: hsa-miR-135a-5p [82]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR135a-5p/AP2alpha /BCL2 signaling pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: AP-2alpha contains a putative miRNA-135a-5p target, which was confirmed as a direct target using the 3'-UTR luciferase reporter system. Additionally, an increase and decrease of miRNA-135a-5p inhi bited or impaired adriamycin-induced apoptosis in BGC-823 cells (p<0.05, compared with the group without gene intervention), respectively. Luciferase reporter experiments confirmed that AP-2alpha bound to the BCL-2 promoter and affected its transcription. Therefore, miRNA-135a-5p increased BCL-2 via AP-2alpha and consequently (+) cell resistance to apoptosis.

Key Molecule: hsa-mir-106a [83]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: TGF-beta signaling pathway; Regulation; hsa04350
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-106a, elevated in multidrug-resistant GC cell lines, suppressed the sensitivity of GC cells to chemo-therapeutic drugs by accelerating drug efflux and reducing apoptosis. Moreover, we validated RUNX3 as a target of miR-106a in GC cells, indicating that miR-106a might modulate MDR by regulating RUNX3 in GC.

Key Molecule: hsa-mir-19a [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: hsa-mir-19b [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Sorcin (SRI) [79]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells.

Key Molecule: FAS-associated death domain protein (FADD) [8]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-633 regulates chemotherapy resistance through downregulating FADD in gastric tumor cells.

Key Molecule: Phosphodiesterase 4D (PDE4D) [80]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: microRNA 494 increases chemosensitivity to doxorubicin in gastric cancer cells by targeting phosphodiesterases 4D.

Key Molecule: Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) [81]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: MAPK/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The restoration of miR-20a expression significantly reduced LRIG1-induced GC cell chemosensitivity.

Key Molecule: Transcription factor AP2 alpha (TFAP2A) [82]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR135a-5p/AP2alpha /BCL2 signaling pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: AP-2alpha contains a putative miRNA-135a-5p target, which was confirmed as a direct target using the 3'-UTR luciferase reporter system. Additionally, an increase and decrease of miRNA-135a-5p inhi bited or impaired adriamycin-induced apoptosis in BGC-823 cells (p<0.05, compared with the group without gene intervention), respectively. Luciferase reporter experiments confirmed that AP-2alpha bound to the BCL-2 promoter and affected its transcription. Therefore, miRNA-135a-5p increased BCL-2 via AP-2alpha and consequently (+) cell resistance to apoptosis.

Key Molecule: Runt-related transcription factor 3 (RUNX3) [83]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: TGF-beta signaling pathway; Regulation; hsa04350
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-106a, elevated in multidrug-resistant GC cell lines, suppressed the sensitivity of GC cells to chemo-therapeutic drugs by accelerating drug efflux and reducing apoptosis. Moreover, we validated RUNX3 as a target of miR-106a in GC cells, indicating that miR-106a might modulate MDR by regulating RUNX3 in GC.

Key Molecule: Phosphatase and tensin homolog (PTEN) [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (D63785) [84]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR422a/MEF2D signaling pathway; Regulation; hsa05206
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA-D6378 mediates gastric cancer cell resistance to apoptosis by modulating the miR-422a-MEF2D signaling pathway and Silencing of Lncr-D63785 enhanced the sensitivity of gastric cancer cells to chemotherapy by inducing apoptosis.

Key Molecule: hsa-miR-422a [84]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR422a/MEF2D signaling pathway; Regulation; hsa05206
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-422a has an enhancer activity in DOX-mediated chemosensitivity and cell death.

Key Molecule: hsa-mir-16 [85]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/AR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Transwell invasion assay; CCK8 assay
• Mechanism Description: The expression of miR16-1 was positively related with the chemosensitivity of GC to adriamycin, and miR16-1 could targeted silence FUBP1 to advance the chemosensitivity to adriamycin in GC.

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [86]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Transwell Invasion assay; Annexin V-FITC apoptosis detection assay
• Mechanism Description: NEAT1 silence in SGC7901 cells could inhibit proliferation and invasion ability, and promote cell apoptosis significantly. NEAT1 knockdown Inhibited Chemotherapy Resistance to Adriamycin in GC Adriamycin-Resistant Cells.

Key Molecule: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [49]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: Silencing LncRNA HULC could enhance chemotherapy induced apoptosis in GC cells.

Key Molecule: hsa-mir-126 [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Caspase3/7 activity assay
• Mechanism Description: microRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2.

Key Molecule: hsa-mir-495 [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Key Molecule: hsa-miR-21-5p [88]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Suppression of miR-21-5p expression sensitizes SGC7901/DOX cells to DOX via upregulating PTEN and TIMP3.

Key Molecule: Protein lin-28 homolog A (CSDD1) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: Protein lin-28 homolog B (CSDD2) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-107 [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-mir-218 [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-218 may inhibit efflux of ADM and oxaliplatin by down-regulating P-gp expression.

Key Molecule: hsa-miR-129-5p [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: Cyclin D binding myb like transcription factor 1 (DMTF1) [92]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay assay
• Mechanism Description: MRUL depletion enhances the chemosensitivity of stomach cancer cells via inhibiting ABCB1 expression and increasing cell apoptosis.

Key Molecule: hsa-mir-185 [66]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Trypan blue exclusion assay; Tunel assay
• Mechanism Description: Restoration of miR-185 alone can inhibit gastric cancer tumor growth. Moreover, combination therapy using enforced miR-185 expression and lower dose chemotherapeutic drugs had an effective therapeutic activity against large established tumors, with decreased host toxicity. miR-185 increases the chemosensitivity of gastric cancer cells in vitro and in vivo. It exerts tumor-suppressing function through negatively regulating ARC. Besides, miR-185 upregulation in response to cisplatin or doxorubicin treatment in gastric cancer cells is dependent on RUNX3 transcriptional activity.

Key Molecule: hsa-miR-520h [93]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: miR-520h is up-regulated by doxorubicin to target HDAC1 and sensitizes gastric cancer cells to doxorubicin, doxorubicin down-regulates HDAC1 expression to aggravate DNA-doxorubicin interaction by inducing the expression of HDAC1-targeting miR-520h.

Key Molecule: hsa-miR-508-5p [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: hsa-mir-27a [94]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Tumorigenesis; Inhibition; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-27a could also confer sensitivity of drugs on gastric cancer cells, and might increase accumulation and decrease releasing amount of adriamycin in gastric cancer cells. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein and the transcriptional activity of cyclin D1, and up-regulate the expression of p21.

Key Molecule: hsa-mir-181 [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: hsa-mir-34 [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: hsa-mir-15b [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Key Molecule: hsa-mir-16 [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [92], [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay assay
• Mechanism Description: MRUL depletion enhances the chemosensitivity of stomach cancer cells via inhibiting ABCB1 expression and increasing cell apoptosis. And The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-218 may inhibit efflux of ADM and oxaliplatin by down-regulating P-gp expression.

Key Molecule: ATP-binding cassette sub-family C5 (ABCC5) [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: ATP-binding cassette sub-family G1 (ABCG1) [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Myocyte-specific enhancer factor 2D (MEF2D) [84]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: miR422a/MEF2D signaling pathway; Regulation; hsa05206
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: MEF2D expression markedly inhibited BGC823 cell proliferation and migration and invasion and enhanced the sensitivity of gastric cancer cells to chemotherapy.

Key Molecule: Far upstream element-binding protein 1 (FUBP1) [85]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/AR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Transwell invasion assay; CCK8 assay
• Mechanism Description: The expression of miR16-1 was positively related with the chemosensitivity of GC to adriamycin, and miR16-1 could targeted silence FUBP1 to advance the chemosensitivity to adriamycin in GC.

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Caspase3/7 activity assay
• Mechanism Description: microRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Key Molecule: Phosphatase and tensin homolog (PTEN) [88]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Suppression of miR-21-5p expression sensitizes SGC7901/DOX cells to DOX via upregulating PTEN and TIMP3.

Key Molecule: Metalloproteinase inhibitor 3 (TIMP3) [88]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Suppression of miR-21-5p expression sensitizes SGC7901/DOX cells to DOX via upregulating PTEN and TIMP3.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Higher miR-218 levels increased the level of Bax and reduced the level of Bcl-2 and miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Key Molecule: Smoothened homolog (SMO) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Higher miR-218 levels increased the level of Bax and reduced the level of Bcl-2 and miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Key Molecule: Activity-regulated cytoskeleton-associated protein (ARC) [66]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Trypan blue exclusion assay; Tunel assay
• Mechanism Description: Restoration of miR-185 alone can inhibit gastric cancer tumor growth. Moreover, combination therapy using enforced miR-185 expression and lower dose chemotherapeutic drugs had an effective therapeutic activity against large established tumors, with decreased host toxicity. miR-185 increases the chemosensitivity of gastric cancer cells in vitro and in vivo. It exerts tumor-suppressing function through negatively regulating ARC. Besides, miR-185 upregulation in response to cisplatin or doxorubicin treatment in gastric cancer cells is dependent on RUNX3 transcriptional activity.

Key Molecule: Histone deacetylase 1 (HDAC1) [93]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: miR-520h is up-regulated by doxorubicin to target HDAC1 and sensitizes gastric cancer cells to doxorubicin, doxorubicin down-regulates HDAC1 expression to aggravate DNA-doxorubicin interaction by inducing the expression of HDAC1-targeting miR-520h.

Key Molecule: DNA-directed RNA polymerase I subunit RPA12 (RPA12) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: G1/S-specific cyclin-D1 (CCND1) [94]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Tumorigenesis; Inhibition; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-27a could also confer sensitivity of drugs on gastric cancer cells, and might increase accumulation and decrease releasing amount of adriamycin in gastric cancer cells. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein and the transcriptional activity of cyclin D1, and up-regulate the expression of p21.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: High mobility group protein HMGI-C (HMGA2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: Neurogenic locus notch homolog protein (NOTCH) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Etoposide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-181 [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Etoposide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: hsa-mir-15b [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Etoposide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Key Molecule: hsa-mir-16 [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Etoposide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Etoposide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Etoposide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Pvt1 oncogene (PVT1) [95]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nod/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: LncRNA PVT1 can inhibit apoptosis and enhance the 5-Fu resistance via Increasing Bcl2 expression in Gastric Cancer.

Key Molecule: Long non-protein coding RNA (XLOC_006753) [9]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Activation; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Long non-coding RNA XLOC_006753 promotes the development of multidrug resistance in gastric cancer cells through the PI3k/Akt/mTOR signaling pathway.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [12]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR; Luciferase reporter assay; Pull down assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells.

Key Molecule: hsa-miR-23b-3p [12]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR; Luciferase reporter assay; Pull down assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. MALAT1 promotes autophagy-associated chemoresistance of GC cells via sequestration of miR23b-3p.

Key Molecule: hsa-mir-145 [16]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: RT-PCR; qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer.

Key Molecule: hsa-mir-27b [22]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/FU cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR27b.

Key Molecule: Urothelial cancer associated 1 (UCA1) [22]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/FU cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: LncRNA urothelial carcinoma associated 1 (UCA1) increases multi-drug resistance of gastric cancer via downregulating miR27b.

Key Molecule: hsa-mir-363 [32]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-363 promotes gastric cancer cells proliferation by inhibiting FBW7 expression and was associated with chemo-resistance of gastric cancer cells. Silencing FBW7 largely phenocopied miR-363-induced resistance to chemotherapy agents and promoted proliferation in gastric cancer cells. In addition, an inverse correlation between miR-363 and FBW7 mRNA expression was observed in gastric cancer tissues.

Key Molecule: hsa-mir-19a [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: hsa-mir-19b [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Transforming growth factor beta 1 (TGFB1) [96]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Key Molecule: hsa-miR-145-5p [96]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Key Molecule: MACC1 antisense RNA 1 (MACC1-AS1) [96]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [95]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nod/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: LncRNA PVT1 can inhibit apoptosis and enhance the 5-Fu resistance via Increasing Bcl2 expression in Gastric Cancer.

Key Molecule: Extracellular matrix receptor III (CD44) [16]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer.

Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7) [32]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-363 promotes gastric cancer cells proliferation by inhibiting FBW7 expression and was associated with chemo-resistance of gastric cancer cells. Silencing FBW7 largely phenocopied miR-363-induced resistance to chemotherapy agents and promoted proliferation in gastric cancer cells. In addition, an inverse correlation between miR-363 and FBW7 mRNA expression was observed in gastric cancer tissues.

Key Molecule: Phosphatase and tensin homolog (PTEN) [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [97]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Bromodeoxyuridine incorporation assay; Flow cytometry assay; Transwell assay
• Mechanism Description: Down-regulation of HOTAIR could promote chemosensitivity, induce apoptosis of GC cells, and significantly inhibit GC cell proliferation, invasion, and metastasis in vivo and in vitro.

Key Molecule: hsa-mir-147 [98]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR147 suppressed the proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-FU by promoting cell apoptosis through directly targeting PTEN and regulating the PI3k/AkT signaling pathway. knockdown of pten reverses the effects of miR147 downregulation on gastric cancer cells.

Key Molecule: hsa-mir-31 [99]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: Induction of miR31 in MkN-45 followed by suppression of RhoA expression resulted in increased sensitivity to 5-fluorouracil, inhibition of cell proliferation, and invasion compared to the control groups.

Key Molecule: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [49]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: Silencing LncRNA HULC could enhance chemotherapy induced apoptosis in GC cells.

Key Molecule: hsa-mir-939 [100]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: RAF/MEK/ERK signaling pathway; Inhibition; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assay; Flow cytometric analysis; Wound-healing, migration and invasion assay
• Mechanism Description: Decreased expression of miR939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEk/ERk pathway. miR939 exerted its function mainly through inhibiting SLC34A2/Raf/MEk/ERk pathway, which is activated in GC.

Key Molecule: hsa-mir-31 [101]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: MkN-45-miR-31 showed an increased sensitivity to 5-FU, decreased migration and cell invasion compared to the control groups and induction of miR-31 expression in MkN-45 caused a significant reduction of E2F6 and SMUG1 genes.

Key Molecule: hsa-mir-31 [102]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: SNU-5 cells; Gastric; Homo sapiens (Human); CVCL_0078
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-31 triggers G 2/M cell cycle arrest, enhances the chemosensitivity and inhibits migration and invasion of human gastric cancer cells by downregulating the expression of zeste homolog 2 (ZH2).

Key Molecule: hsa-mir-495 [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Key Molecule: hsa-miR-195-5p [103]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR 195 5p inhibit multi drug resistance of gastric cancer cells via downregulating ZNF139.

Key Molecule: hsa-miR-623 [104]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The restored miR-623 expression could inhibit the proliferation of GC cells and enhance their chemosensitivity to 5-FU via the cell apoptosis pathway and the recovered CCND1 expression counteracted the effects of miR-623 on GC cell proliferation, chemosensitivity, and 5-FU-induced apoptosis.

Key Molecule: Protein lin-28 homolog A (CSDD1) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: Protein lin-28 homolog B (CSDD2) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-107 [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-mir-218 [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-218 may inhibit efflux of ADM and oxaliplatin by down-regulating P-gp expression.

Key Molecule: hsa-mir-197 [105]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: When miR-197 was overexpressed in SGC7901 cells, the protein levels of MAPk1 were downregulated. Furthermore, MAPk1 knockdown significantly increased the growth inhibition rate of the SGC7901/5-FU cells compared with those in the control group. These results indicated that miR-197 may influence the sensitivity of 5-FU treatment in a gastric cancer cell line by targeting MAPk1.

Key Molecule: hsa-miR-23b-3p [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: SCID-SHO mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: hsa-miR-508-5p [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: hsa-mir-204 [106]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: GTL-16 cells; Gastric; Homo sapiens (Human); CVCL_7668
• In Vivo Model: CD1 nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil.

Key Molecule: hsa-mir-27a [94]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Tumorigenesis; Inhibition; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-27a could also confer sensitivity of drugs on gastric cancer cells, and might increase accumulation and decrease releasing amount of adriamycin in gastric cancer cells. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein and the transcriptional activity of cyclin D1, and up-regulate the expression of p21.

Key Molecule: hsa-mir-181 [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Solute carrier family 34 member 2 (SLC34A2) [100]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: RAF/MEK/ERK signaling pathway; Inhibition; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Colony formation assay; Flow cytometric analysis; Wound-healing, migration and invasion assay
• Mechanism Description: Decreased expression of miR939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEk/ERk pathway. miR939 exerted its function mainly through inhibiting SLC34A2/Raf/MEk/ERk pathway, which is activated in GC.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-218 may inhibit efflux of ADM and oxaliplatin by down-regulating P-gp expression.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-mir-30a [75]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR30a can decrease multidrug resistance (MDR) of gastric cancer cells, miR30a overexpression decreased the expression of P-gp, a MDR-related protein. It is also an important miRNA modulating EMT of the cancer cells.

Key Molecule: Death effector domain-containing protein (DEDD) [76]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, impairing EMT in GC cells.

Key Molecule: hsa-mir-17 [76]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, impairing EMT in GC cells.

Key Molecule: TGF-beta receptor type II (TGFBR2) [107]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: TGF-beta signaling pathway; Inhibition; hsa04350
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Caspase 3 assay kit
• Mechanism Description: Sensitization of Gastric Cancer Cells to 5-FU by microRNA-204 Through Targeting the TGFBR2-Mediated Epithelial to Mesenchymal Transition.

Key Molecule: hsa-mir-204 [107]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: TGF-beta signaling pathway; Inhibition; hsa04350
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Caspase 3 assay kit
• Mechanism Description: Sensitization of Gastric Cancer Cells to 5-FU by microRNA-204 Through Targeting the TGFBR2-Mediated Epithelial to Mesenchymal Transition.

Key Molecule: Long non-protein coding RNA (LEIGC) [108]

• Sensitive Disease: Gastric carcinoma [ICD-11: 2B72.Z]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Overexpression of LEIGC suppressed tumor growth and cell proliferation, and (+) the sensitivity of gastric cancer cells to 5-fluorouracil (5-FU), whereas knockdown of LEIGC showed the opposite effect. We further demonstrated LEIGC functions by inhibiting the epithelial-to-mesenchymal transition (EMT) in gastric cancer.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatase and tensin homolog (PTEN) [98]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR147 suppressed the proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-FU by promoting cell apoptosis through directly targeting PTEN and regulating the PI3k/AkT signaling pathway. knockdown of pten reverses the effects of miR147 downregulation on gastric cancer cells.

Key Molecule: Transforming protein RhoA (RHOA) [99]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis; Immunohistochemical assay
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: Induction of miR31 in MkN-45 followed by suppression of RhoA expression resulted in increased sensitivity to 5-fluorouracil, inhibition of cell proliferation, and invasion compared to the control groups.

Key Molecule: Transcription factor E2F6 (E2F6) [101]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: MkN-45-miR-31 showed an increased sensitivity to 5-FU, decreased migration and cell invasion compared to the control groups and induction of miR-31 expression in MkN-45 caused a significant reduction of E2F6 and SMUG1 genes.

Key Molecule: Single-strand selective monofunctional uracil DNA glycosylase (SMUG1) [101]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: MkN-45-miR-31 showed an increased sensitivity to 5-FU, decreased migration and cell invasion compared to the control groups and induction of miR-31 expression in MkN-45 caused a significant reduction of E2F6 and SMUG1 genes.

Key Molecule: Zeste homolog 2 (ZH2) [102]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: SNU-5 cells; Gastric; Homo sapiens (Human); CVCL_0078
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-31 triggers G 2/M cell cycle arrest, enhances the chemosensitivity and inhibits migration and invasion of human gastric cancer cells by downregulating the expression of zeste homolog 2 (ZH2).

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Key Molecule: Zinc finger protein with KRAB and SCAN domains 1 (ZKSCAN1) [103]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR 195 5p inhibit multi drug resistance of gastric cancer cells via downregulating ZNF139.

Key Molecule: G1/S-specific cyclin-D1 (CCND1) [104]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: The restored miR-623 expression could inhibit the proliferation of GC cells and enhance their chemosensitivity to 5-FU via the cell apoptosis pathway and the recovered CCND1 expression counteracted the effects of miR-623 on GC cell proliferation, chemosensitivity, and 5-FU-induced apoptosis.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Higher miR-218 levels increased the level of Bax and reduced the level of Bcl-2 and miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Key Molecule: Smoothened homolog (SMO) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Higher miR-218 levels increased the level of Bax and reduced the level of Bcl-2 and miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Key Molecule: Mitogen-activated protein kinase 1 (MAPK1) [105]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: When miR-197 was overexpressed in SGC7901 cells, the protein levels of MAPk1 were downregulated. Furthermore, MAPk1 knockdown significantly increased the growth inhibition rate of the SGC7901/5-FU cells compared with those in the control group. These results indicated that miR-197 may influence the sensitivity of 5-FU treatment in a gastric cancer cell line by targeting MAPk1.

Key Molecule: Ubiquitin-like protein ATG12 (ATG12) [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: High mobility group protein B2 (HMGB2) [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: DNA-directed RNA polymerase I subunit RPA12 (RPA12) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [106]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: GTL-16 cells; Gastric; Homo sapiens (Human); CVCL_7668
• In Vivo Model: CD1 nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil.

Key Molecule: G1/S-specific cyclin-D1 (CCND1) [94]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Tumorigenesis; Inhibition; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-27a could also confer sensitivity of drugs on gastric cancer cells, and might increase accumulation and decrease releasing amount of adriamycin in gastric cancer cells. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein and the transcriptional activity of cyclin D1, and up-regulate the expression of p21.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Gemcitabine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-34 [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Gemcitabine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Gemcitabine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: High mobility group protein HMGI-C (HMGA2) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Gemcitabine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Key Molecule: Neurogenic locus notch homolog protein (NOTCH) [73]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Gemcitabine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Human gastric cancer kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor, miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.

Lapatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-494 [109]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Lapatinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: YCC1 cells; Gastric; Homo sapiens (Human); CVCL_9646
• In Vitro Model: YCC1-F cells; Gastric; Homo sapiens (Human); CVCL_9646
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR 494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2 positive gastric cancer.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [109]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Lapatinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: YCC1 cells; Gastric; Homo sapiens (Human); CVCL_9646
• In Vitro Model: YCC1-F cells; Gastric; Homo sapiens (Human); CVCL_9646
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR 494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2 positive gastric cancer.

Mitomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hypoxia-inducible factor 2-alpha (EPAS1) [78]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Mitomycin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Over-expression of EPAS-1 increased the expression of PXR responsive genes, enhanced the proliferation of BGC-823 cells and boosted the resistance of BGC-823 cells against the cytotoxicity of chemotherapeutic drugs, e.g. Mitomycin C and Paclitaxel.EPAS-1 reduces BGC-823 cell apoptosis induced by Mitomycin C and Paclitaxel.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-495 [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Mitomycin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [53]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Mitomycin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-135a [110]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Sp1/DAPK2 signaling signaling pathway; Inhibition; hsa05231
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MGC-803/OXA cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901/OXA cells; Gastric; Homo sapiens (Human); CVCL_B0A1
• In Vitro Model: SNU-5 cells; Gastric; Homo sapiens (Human); CVCL_0078
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR135a promotes gastric cancer progression and resistance to oxaliplatin. The mechanism whereby miR135a promotes GC pathogenesis appears to be the suppression of E2F1 expression and Sp1/DAPk2 pathway signaling.

Key Molecule: BLACAT1 overlapping LEMD1 locus (BLACAT1) [111]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BLACAT1/miR361/ABCB1 signaling pathway; Regulation; hsa05206
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Key Molecule: BLACAT1 overlapping LEMD1 locus (BLACAT1) [111]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: miR125a/hexokinase 2 pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Key Molecule: hsa-mir-361 [111]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BLACAT1/miR361/ABCB1 signaling pathway; Regulation; hsa05206
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [111]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: miR125a/hexokinase 2 pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [111]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: miR125a/hexokinase 2 pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell assay
• Mechanism Description: BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Transforming growth factor beta 1 (TGFB1) [96]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Key Molecule: hsa-miR-145-5p [96]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Key Molecule: MACC1 antisense RNA 1 (MACC1-AS1) [96]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Transcription factor E2F1 (E2F1) [110]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Sp1/DAPK2 signaling signaling pathway; Inhibition; hsa05231
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MGC-803/OXA cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901/OXA cells; Gastric; Homo sapiens (Human); CVCL_B0A1
• In Vitro Model: SNU-5 cells; Gastric; Homo sapiens (Human); CVCL_0078
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR135a promotes gastric cancer progression and resistance to oxaliplatin. The mechanism whereby miR135a promotes GC pathogenesis appears to be the suppression of E2F1 expression and Sp1/DAPk2 pathway signaling.

Key Molecule: Sphingosine-1-phosphate lyase 1 (SGPL1) [43]

• Resistant Disease: Gastric cardia adenocarcinoma [ICD-11: 2B72.2]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: S1P could lead to cytotoxic drug resistance in gastroesophegal cancer acting in an autocrine or paracrine manner via cell surface S1P receptors following transportation out of the cytosol. Alternatively S1P may mediate cytotoxic drug resistance acting intracellularly by counteracting apoptosis mediated by its pro-apoptotic precursor ceramide or interaction with known intracellular targets involved in cancer pathogenesis and cytotoxic drug resistance such as Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC 2) to which S1P directly binds and inhibits, and TNF Receptor-Associated Factor 2 (TRAF 2), or Protein Kinase C (PKC). S1P production controlled by SPHK1 and SGPL1 are key determinants of cytotoxic drug resistance and that decreasing S1P production in cancer cells could lead to increased cytotoxic sensitivity.

Key Molecule: Sphingosine kinase 1 (SPHK1) [43]

• Resistant Disease: Gastric cardia adenocarcinoma [ICD-11: 2B72.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: S1P could lead to cytotoxic drug resistance in gastroesophegal cancer acting in an autocrine or paracrine manner via cell surface S1P receptors following transportation out of the cytosol. Alternatively S1P may mediate cytotoxic drug resistance acting intracellularly by counteracting apoptosis mediated by its pro-apoptotic precursor ceramide or interaction with known intracellular targets involved in cancer pathogenesis and cytotoxic drug resistance such as Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC 2) to which S1P directly binds and inhibits, and TNF Receptor-Associated Factor 2 (TRAF 2), or Protein Kinase C (PKC). S1P production controlled by SPHK1 and SGPL1 are key determinants of cytotoxic drug resistance and that decreasing S1P production in cancer cells could lead to increased cytotoxic sensitivity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-195-5p [103]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR 195 5p inhibit multi drug resistance of gastric cancer cells via downregulating ZNF139.

Key Molecule: Protein lin-28 homolog A (CSDD1) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: Protein lin-28 homolog B (CSDD2) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-107 [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-mir-218 [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-218 may inhibit efflux of ADM and oxaliplatin by down-regulating P-gp expression.

Key Molecule: hsa-mir-204 [106]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: GTL-16 cells; Gastric; Homo sapiens (Human); CVCL_7668
• In Vivo Model: CD1 nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-218 may inhibit efflux of ADM and oxaliplatin by down-regulating P-gp expression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Zinc finger protein with KRAB and SCAN domains 1 (ZKSCAN1) [103]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR 195 5p inhibit multi drug resistance of gastric cancer cells via downregulating ZNF139.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Higher miR-218 levels increased the level of Bax and reduced the level of Bcl-2 and miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Key Molecule: Smoothened homolog (SMO) [90]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Higher miR-218 levels increased the level of Bax and reduced the level of Bcl-2 and miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [106]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Oxaliplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: GTL-16 cells; Gastric; Homo sapiens (Human); CVCL_7668
• In Vivo Model: CD1 nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil.

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-590-5p [21]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Activation; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay; Matrigel transwell assay
• Mechanism Description: miR590-5p regulates gastric cancer cell growth and chemosensitivity through RECk and the AkT/ERk pathway. RECk is a direct target of miR590-5p, knockdown of RECk accelerated cell proliferation and motility and decreased the drug sensitivity.The AkT/ERk and STAT3 signaling pathways were activated by miR590-5p overexpression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) [21]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Activation; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Matrigel transwell assay
• Mechanism Description: miR590-5p regulates gastric cancer cell growth and chemosensitivity through RECk and the AkT/ERk pathway. RECk is a direct target of miR590-5p, knockdown of RECk accelerated cell proliferation and motility and decreased the drug sensitivity.The AkT/ERk and STAT3 signaling pathways were activated by miR590-5p overexpression.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Protein lin-28 homolog A (CSDD1) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: Protein lin-28 homolog B (CSDD2) [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-107 [89]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; hsa05206
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-34c-5p [112]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MAPT is a microtubule-associated protein which promotes the assembly of tubulin into microtubules to stabilize microtubule structure. Reduced expression of MAPT has been also associated with a better response to paclitaxel in gastric cancer patients, reduced expression of miR-34c-5p, provides a possible mechanism of paclitaxel resistance in gastric cancer, overexpression of miR-34c-5p reduces MAPT expression and restores paclitaxel sensitivity.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-miR-155-5p [113]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Key Molecule: Trans-acting T-cell-specific transcription factor GATA-3 (GATA3) [113]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Key Molecule: Tumor protein p53-inducible nuclear protein 1 (TP53INP1) [113]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Key Molecule: Catenin beta-1 (CTNNB1) [77]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Regulation; hsa04310
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Silencing of ZFAS1 augmented the sensitivity to cis-platinum or paclitaxel in gastric cancer cancer cells and silencing of ZFAS1-induced inhibition of malignancies was reversed by beta-catenin.

Key Molecule: ZNFX1 antisense RNA 1 (ZFAS1) [77]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Regulation; hsa04310
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Silencing of ZFAS1 augmented the sensitivity to cis-platinum or paclitaxel in gastric cancer cancer cells and silencing of ZFAS1-induced inhibition of malignancies was reversed by beta-catenin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Microtubule-associated protein tau (MAPT) [112]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MAPT is a microtubule-associated protein which promotes the assembly of tubulin into microtubules to stabilize microtubule structure. Reduced expression of MAPT has been also associated with a better response to paclitaxel in gastric cancer patients, reduced expression of miR-34c-5p, provides a possible mechanism of paclitaxel resistance in gastric cancer, overexpression of miR-34c-5p reduces MAPT expression and restores paclitaxel sensitivity.

Palbociclib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Cyclin-dependent kinase inhibitor 2A (CDKN2A) [114]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Nonsense; p.R80* (c.238C>T)
• Sensitive Drug: Palbociclib
• Experimental Note: Identified from the Human Clinical Data

Rhodium trichloride hydrate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [115]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Up-regulation; Expression
• Resistant Drug: Rhodium trichloride hydrate
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Western bloting analysis; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: METase/LncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy.

Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [116]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Trastuzumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-223 [117]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Trastuzumab
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: miR223/FBXW7 signaling pathway; Regulation; hsa05206
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• In Vitro Model: NUGC4 cells; Gastric; Homo sapiens (Human); CVCL_3082
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of GC cells to trastuzumab, while suppression of miR-223 restored FBXW7 expression and the sensitivity of GC cells to trastuzumab.

Key Molecule: hsa-mir-21 [118]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Trastuzumab
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR21/PTEN signaling pathway; Activation; hsa05206
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC4 cells; Gastric; Homo sapiens (Human); CVCL_3082
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The miR-21/PTEN pathway regulated the sensitivity of HER2-positive GC cell lines to trastuzumab through modulation apoptosis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7) [117]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Trastuzumab
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: miR223/FBXW7 signaling pathway; Regulation; hsa05206
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• In Vitro Model: NUGC4 cells; Gastric; Homo sapiens (Human); CVCL_3082
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of GC cells to trastuzumab, while suppression of miR-223 restored FBXW7 expression and the sensitivity of GC cells to trastuzumab.

Key Molecule: Phosphatase and tensin homolog (PTEN) [118]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Trastuzumab
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR21/PTEN signaling pathway; Activation; hsa05206
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC4 cells; Gastric; Homo sapiens (Human); CVCL_3082
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The miR-21/PTEN pathway regulated the sensitivity of HER2-positive GC cell lines to trastuzumab through modulation apoptosis.

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-1 [79]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells.

Key Molecule: hsa-mir-20a [81]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: MAPK/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The restoration of miR-20a expression significantly reduced LRIG1-induced GC cell chemosensitivity.

Key Molecule: hsa-mir-106a [83]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: TGF-beta signaling pathway; Regulation; hsa04350
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-106a, elevated in multidrug-resistant GC cell lines, suppressed the sensitivity of GC cells to chemo-therapeutic drugs by accelerating drug efflux and reducing apoptosis. Moreover, we validated RUNX3 as a target of miR-106a in GC cells, indicating that miR-106a might modulate MDR by regulating RUNX3 in GC.

Key Molecule: hsa-mir-19a [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: hsa-mir-19b [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: hsa-mir-200b [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: hsa-mir-200c [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: hsa-miR-429 [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Sorcin (SRI) [79]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells.

Key Molecule: Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) [81]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: MAPK/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The restoration of miR-20a expression significantly reduced LRIG1-induced GC cell chemosensitivity.

Key Molecule: Runt-related transcription factor 3 (RUNX3) [83]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: TGF-beta signaling pathway; Regulation; hsa04350
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-106a, elevated in multidrug-resistant GC cell lines, suppressed the sensitivity of GC cells to chemo-therapeutic drugs by accelerating drug efflux and reducing apoptosis. Moreover, we validated RUNX3 as a target of miR-106a in GC cells, indicating that miR-106a might modulate MDR by regulating RUNX3 in GC.

Key Molecule: Phosphatase and tensin homolog (PTEN) [39]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: PTEN/AKT signaling pathway; Inhibition; hsa05235
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-19a/b are upregulated in multidrug-resistant gastric cancer cell line, miR-19a/b suppress the sensitivity of gastric cancer cells to anticancer drugs, miR-19a/b accelerate the efflux of ADR through P-gp upregulation.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [41]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Fas/FasL signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The anti-apoptotic protein BCL2 and XIAP were upregulated, while the miR-200bc/429 cluster was downregulated in both SGC7901/VCR and A549/CDDP cells. miR-200bc/429 cluster might play an important role in the development of MDR in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes BCL2 and XIAP.

Key Molecule: Heat shock protein beta-1 (HSPB1) [119]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: Increased expression of HSP27 is linked to vincristine-resistance in gastric cancer.

Key Molecule: Sorcin (SRI) [120]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The elevated sorcin expression could contribute considerably to the vincristine resistance in SGC7901/VCR. The overexpression of sorcin was involved in the MDR phenotype of SGC7901/VCR possibly by inhibiting vincristine-induced cell apoptosis.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-647 [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [12]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. MALAT1 promotes autophagy-associated chemoresistance of GC cells via sequestration of miR23b-3p.

Key Molecule: hsa-miR-23b-3p [12]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: RT-PCR; Luciferase reporter assay; Pull down assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 acts as a competing endogenous RNA for miR23b-3p and attenuates the inhibitory effect of miR23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. MALAT1 promotes autophagy-associated chemoresistance of GC cells via sequestration of miR23b-3p.

Key Molecule: hsa-mir-101 [46]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: p38/MAPK/AKT signaling pathway; Regulation; hsa04010
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR101 alleviates chemoresistance of gastric cancer cells by targeting ANXA2, ectopic expression of ANXA2 reversed the effect of miR101 on P-gp expression, cell viability and apoptosis. knockdown of ANXA2 increased sensitivity to doxorubicin, 5-FU and DDP by regulating p38MAPk and AkT pathways.

Key Molecule: hsa-mir-126 [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Caspase3/7 activity assay
• Mechanism Description: microRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2.

Key Molecule: hsa-miR-1284 [122]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-1284 overexpression can regulate the response of SGC7901/VCR cells to chemotherapeutic resistance by targeting EIF4A1, reducing JUN and MMP12, and increasing MYC.

Key Molecule: hsa-miR-23b-3p [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: SCID-SHO mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: hsa-miR-129-5p [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: Cyclin D binding myb like transcription factor 1 (DMTF1) [92]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay assay
• Mechanism Description: MRUL depletion enhances the chemosensitivity of stomach cancer cells via inhibiting ABCB1 expression and increasing cell apoptosis.

Key Molecule: hsa-miR-508-5p [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: hsa-mir-27a [94]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Tumorigenesis; Inhibition; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-27a could also confer sensitivity of drugs on gastric cancer cells, and might increase accumulation and decrease releasing amount of adriamycin in gastric cancer cells. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein and the transcriptional activity of cyclin D1, and up-regulate the expression of p21.

Key Molecule: hsa-mir-497 [71]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Enforced miR-497 expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, has-miR-497 could play a role in both gastric and lung cancer cell lines at least in part by modulation of apoptosis via targeting BCL2.

Key Molecule: hsa-mir-181 [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: hsa-mir-15b [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Key Molecule: hsa-mir-16 [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [92], [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay assay
• Mechanism Description: MRUL depletion enhances the chemosensitivity of stomach cancer cells via inhibiting ABCB1 expression and increasing cell apoptosis. And The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: ATP-binding cassette sub-family C5 (ABCC5) [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: ATP-binding cassette sub-family G1 (ABCG1) [91]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Macrophage metalloelastase (MMP12) [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Key Molecule: Collagenase 72 kDa type IV collagenase (MMP2) [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ankyrin-2 (ANK2) [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Key Molecule: Extracellular matrix receptor III (CD44) [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Key Molecule: Focal adhesion kinase 1 (FAK1) [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Key Molecule: Zinc finger protein SNAI1 (SNAI1) [121]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay; Wound healing and transwell assay
• Mechanism Description: Overexpression of miR647 sensitizes tumors to chemotherapy in vivo by reducing the expression levels of ANk2, FAk, MMP2, MMP12, CD44 and SNAIL1.

Key Molecule: Annexin A2 (ANXA2) [46]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: p38/MAPK/AKT signaling pathway; Regulation; hsa04010
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RIP assay; Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR101 alleviates chemoresistance of gastric cancer cells by targeting ANXA2, ectopic expression of ANXA2 reversed the effect of miR101 on P-gp expression, cell viability and apoptosis. knockdown of ANXA2 increased sensitivity to doxorubicin, 5-FU and DDP by regulating p38MAPk and AkT pathways.

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Caspase3/7 activity assay
• Mechanism Description: microRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2.

Key Molecule: Eukaryotic initiation factor 4A-I (EIF4A1) [122]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-1284 overexpression can regulate the response of SGC7901/VCR cells to chemotherapeutic resistance by targeting EIF4A1, reducing JUN and MMP12, and increasing MYC.

Key Molecule: Ubiquitin-like protein ATG12 (ATG12) [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: High mobility group protein B2 (HMGB2) [62]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR23b-3p/ATG12/HMGB2/autophagy regulatory loop signaling pathway; Regulation; hsa05206
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

Key Molecule: DNA-directed RNA polymerase I subunit RPA12 (RPA12) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Key Molecule: G1/S-specific cyclin-D1 (CCND1) [94]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Down-regulation of miR-27a could also confer sensitivity of drugs on gastric cancer cells, and might increase accumulation and decrease releasing amount of adriamycin in gastric cancer cells. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein and the transcriptional activity of cyclin D1, and up-regulate the expression of p21.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [72]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [74]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vincristine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.

Clinical Trial Drug(s) 7 drug(s) in total

Capivasertib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: PI3-kinase alpha (PIK3CA) [123]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: Capivasertib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Stomach; .
• In Vivo Model: GC xenograft (PDGCX) mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay

Cucurbitacin B

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Gastric cancer associated transcript 3 (GACAT3) [124]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cucurbitacin B
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: GACAT3 alleviates the anticancer drug cucurbitacin B-induced apoptosis of gastric cancer cells via increasing STAT3 expression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Signal transducer activator transcription 3 (STAT3) [124]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cucurbitacin B
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: GACAT3 alleviates the anticancer drug cucurbitacin B-induced apoptosis of gastric cancer cells via increasing STAT3 expression.

Selumetinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [125]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Drug: Selumetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NUGC-4 cells; Lymph node; Homo sapiens (Human); CVCL_3082/CVCL_8372
• Experiment for Molecule Alteration: Multiplex deep sequencing of MAP2K1 cDNAs assay
• Experiment for Drug Resistance: Focus formation assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by aberration of the drug's therapeutic target

TRAIL

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-942 [126]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: TRAIL
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interferon alpha-inducible protein 27 (IFI27) [126]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: TRAIL
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-494 [127]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: TRAIL
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Down-regulation of Survivin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Baculoviral IAP repeat-containing protein 5 (BIRC5) [127]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: TRAIL
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Down-regulation of Survivin.

Luteolin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-34 [128]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Luteolin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: p53/p21 /MAPK/ERK signaling pathway; Regulation; hsa04115
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: miR34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting Hk1. miR34a overexpression could inhibit GC cells and induce G1 phase arrest via p53/p21 and MAPk /ERk pathways.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hexokinase-1 (HK1) [128]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Luteolin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: p53/p21 /MAPK/ERK signaling pathway; Regulation; hsa04115
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Dual luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis
• Mechanism Description: miR34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting Hk1. miR34a overexpression could inhibit GC cells and induce G1 phase arrest via p53/p21 and MAPk /ERk pathways.

Solamargine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [129]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Solamargine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: IncuCyte ZOOM Live-Cell analysis; TUNEL assay; Flow cytometry assay
• Mechanism Description: Solamargine increased the expression of lncNEAT1_2 via the inhibition of Erk1/2 MAPk signaling and promoted the apoptosis of GC cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mitogen-activated protein kinase 1 (MAPK1) [129]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Solamargine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: IncuCyte ZOOM Live-Cell analysis; TUNEL assay; Flow cytometry assay
• Mechanism Description: Solamargine increased the expression of lncNEAT1_2 via the inhibition of Erk1/2 MAPk signaling and promoted the apoptosis of GC cells.

Key Molecule: Mitogen-activated protein kinase 1 (MAPK1) [129]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Solamargine
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: IncuCyte ZOOM Live-Cell analysis; TUNEL assay; Flow cytometry assay
• Mechanism Description: Solamargine increased the expression of lncNEAT1_2 via the inhibition of Erk1/2 MAPk signaling and promoted the apoptosis of GC cells.

Trichostatin A

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-199a-5p [130]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Trichostatin A
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: RT-PCR; qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: GRP78 up-regulation is a major contributor to tumorigenesis and therapeutic resistance, miR-30d, miR-181a and miR-199a-5p regulate GRP78 and that their decreased expression in tumor cells results in increased GRP78 levels, which in turn promotes tumorigenesis and therapeutic resistance.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Endoplasmic reticulum chaperone BiP (HSPA5) [130]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Trichostatin A
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: GRP78 up-regulation is a major contributor to tumorigenesis and therapeutic resistance, miR-30d, miR-181a and miR-199a-5p regulate GRP78 and that their decreased expression in tumor cells results in increased GRP78 levels, which in turn promotes tumorigenesis and therapeutic resistance.

Preclinical Drug(s) 1 drug(s) in total

Glesatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.Y1230C (c.3689A>G)
• Sensitive Drug: Glesatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NCI-H441 cells; Lung; Homo sapiens (Human); CVCL_1561
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: SNU638 cells; Ascites; Homo sapiens (Human); CVCL_0102
• In Vitro Model: NCI-H596 cells; Lung; Homo sapiens (Human); CVCL_1571
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vivo Model: Nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis

Investigative Drug(s) 6 drug(s) in total

Cardamonin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Pvt1 oncogene (PVT1) [131]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Cardamonin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Cardamonin exerts anti-gastric cancer activity via inhibiting LncRNA-PVT1-STAT3 axis.

Dabrafenib/Trametinib/Vemurafenib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [132]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: Dabrafenib/Trametinib/Vemurafenib
• Experimental Note: Identified from the Human Clinical Data

DX-8951

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [133]

• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: DX-8951
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gastric cancers tissue; .
• Experiment for Molecule Alteration: Luciferase assay; Western bloting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HOTAIR can not only promote tumor proliferation, but also enhances the resistance of tumor cells to drugs.

EAP Protocol

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [134]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.R282L (c.845G>T)
• Sensitive Drug: EAP Protocol
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Stomach; .
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.R282L (c.845G>T) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [134]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Sensitive Drug: EAP Protocol
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Stomach; .
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [134]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Missense mutation; p.R213P (c.638G>C)
• Sensitive Drug: EAP Protocol
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Stomach; .
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.R213P (c.638G>C) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway

MET inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [135]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Molecule Alteration: Copy number gain; .
• Sensitive Drug: MET inhibitors
• Experimental Note: Identified from the Human Clinical Data

Platinum

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (FAM84B-AS) [136]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Platinum
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: NU/NU nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Long non-coding RNA FAM84B-AS promotes resistance of gastric cancer to platinum drugs through inhibition of FAM84B expression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein LRATD2 (LRATD2) [136]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Platinum
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: HGC27 cells; Gastric; Homo sapiens (Human); CVCL_1279
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vivo Model: NU/NU nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Long non-coding RNA FAM84B-AS promotes resistance of gastric cancer to platinum drugs through inhibition of FAM84B expression.

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