Molecule Information

General Information of the Molecule (ID: Mol00029)

Name	Apoptosis regulator Bcl-2 (BCL2) ,Homo sapiens
Molecule Type	Protein
Gene Name	BCL2
Gene ID	596
Location	chr18:63123346-63320128[-]
Sequence	MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPA ASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLH LTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY LNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK Click to Show/Hide
Function	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function. May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release. Click to Show/Hide
Uniprot ID	BCL2_HUMAN
Ensembl ID	ENSG00000171791
HGNC ID	HGNC:990
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

ADTT: Aberration of the Drug's Therapeutic Target

EADR: Epigenetic Alteration of DNA, RNA or Protein

RTDM: Regulation by the Disease Microenvironment

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

25 drug(s) in total

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Berberine

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Colorectal cancer				[1]
Sensitive Disease	Colorectal cancer [ICD-11: 2B91.1]			Disease Info
Sensitive Drug	Berberine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	HT29 Cells	Colon	Homo sapiens (Human)	CVCL_A8EZ
	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	LncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.

Bortezomib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Multiple myeloma				[2]
Sensitive Disease	Multiple myeloma [ICD-11: 2A83.0]			Disease Info
Sensitive Drug	Bortezomib			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell colony		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	U266 cells	Bone marrow	Homo sapiens (Human)	CVCL_0566
	RPMI-8226 cells	Peripheral blood	Homo sapiens (Human)	CVCL_0014
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	microRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2.

Cetuximab

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Colon cancer				[3]
Sensitive Disease	Colon cancer [ICD-11: 2B90.1]			Disease Info
Sensitive Drug	Cetuximab			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	EGFR/RAS/MAPK signaling pathway		Regulation	hsa01521
In Vitro Model	SW480 cells	Colon	Homo sapiens (Human)	CVCL_0546
	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	The extent of caspase and nuclear fragmentation inhibition was higher in cells overexpressing miR-143 or miR-145, which also display reduced Bcl-2 protein steady-state levels. restoration of miR-143 or miR-145 reduces the aggressiveness of mutant kRAS HCT116 cells. In addition, forced expression of these miRNAs in both mutant and wild-type kRAS colon cancer cells increased their sensitivity to cetuximab by increasing cetuximab-mediated ADCC. Moreover, increased levels of effector cell-mediated caspase-dependent apoptosis were observed for mutant kRAS HCT116 miRNAs-overexpressing cells.

Cisplatin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Gastric cancer				[4]
Resistant Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Cervical cancer				[5]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	There was a protective role of miR-7-5p in cervical cancer cells treated with cisplatin and that miR-7-5p expression.miR-7-5p reduced energy consumption via inhibiting PARP-1 expression, and miR-7-5p increased energy generation by suppressing the expression of Bcl-2.
Disease Class: Osteosarcoma				[6]
Resistant Disease	Osteosarcoma [ICD-11: 2B51.0]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	BCL2/cyclin D1 signaling pathway		Inhibition	hsa04210
	Cell apoptosis		Inhibition	hsa04210
	Cell viability		Activation	hsa05200
In Vitro Model	MG63 cells	Bone marrow	Homo sapiens (Human)	CVCL_0426
	SAOS-2 cells	Bone marrow	Homo sapiens (Human)	CVCL_0548
	HOS cells	Bone	Homo sapiens (Human)	CVCL_0312
	143B cells	Bone	Homo sapiens (Human)	CVCL_2270
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	The miR-34c inhibitor restored the BCL-2 and cyclin D1 levels in MG63 and HOS cell line, which implicated that NEAT1 inhibited the tumor suppressor miR-34c and up-regulated cell survival signals for the development of OS.
Disease Class: Non-small cell lung cancer				[7]
Resistant Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell viability		Activation	hsa05200
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	H1299 cells	Lung	Homo sapiens (Human)	CVCL_0060
	NCI-H358 cells	Lung	Homo sapiens (Human)	CVCL_1559
	CL1-0 cells	Lung	Homo sapiens (Human)	CVCL_3871
	H23 cells	Lung	Homo sapiens (Human)	CVCL_1547
	TL4 cells	Lung	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	Patients with tumors expressing low miR-630, high Bcl-2, and a combination of both were more likely than their counterparts to show unfavorable responses to cisplatin-based chemotherapy.
Disease Class: Non-small cell lung cancer				[8]
Resistant Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-21 decreased the expression of PTEN and increased Bcl-2 in A549. Upregulation of miR-21 induces cholangiocarcinoma cell survival and gemcitabine resistance primarily through targeting the PTEN dependent PI3k/Akt pathway. Inhibition of miR-21 was shown to increase the sensitivity to topotecan in breast cancer cells partly by regulating BCL2 induced anti-apoptosis indirectly in MCF-7 cells.
Disease Class: Gastric adenocarcinoma				[9]
Resistant Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Fas/FasL signaling pathway		Regulation	hsa04210
In Vitro Model	SGC7901 cells	Gastric	Homo sapiens (Human)	CVCL_0520
	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.
Disease Class: Lung cancer				[9]
Resistant Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Fas/FasL signaling pathway		Regulation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Disease Class: Lung small cell carcinoma				[10]
Sensitive Disease	Lung small cell carcinoma [ICD-11: 2C25.2]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	16HBE cells	Lung	Homo sapiens (Human)	CVCL_0112
	H446 cells	Lung	Homo sapiens (Human)	CVCL_1562
	H69 cells	Lung	Homo sapiens (Human)	CVCL_8121
	H69AR cells	Lung	Homo sapiens (Human)	CVCL_3513
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay; RT-qPCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR216a.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Ovarian cancer				[11]
Sensitive Disease	Ovarian cancer [ICD-11: 2C73.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	SkOV3 cells	Ovary	Homo sapiens (Human)	CVCL_0532
	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	OVCAR3 cells	Ovary	Homo sapiens (Human)	CVCL_0465
Experiment for Molecule Alteration	Western blot analysis; Dual luciferase reporter assay
Experiment for Drug Resistance	MTT and DAPI assays
Mechanism Description	miR509-3p could sensitize ovarian cancer cells to cisplatin treatment by targeting multiple anti-apoptosis genes including BCL2 and promoteing apoptosis in cancer cells.
Disease Class: Hepatocellular carcinoma				[12]
Sensitive Disease	Hepatocellular carcinoma [ICD-11: 2C12.2]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	BEL-7402 cells	Liver	Homo sapiens (Human)	CVCL_5492
	HL-7702 cells	Liver	Homo sapiens (Human)	CVCL_6926
Experiment for Molecule Alteration	Western blot analysis; Dual luciferase activity assay; qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR503 may enhance the sensitivity of BEL-7402 cells to cisplatin and inhibit the cell proliferation by targeting bcl-2. miR503 could interact with bcl-2 and inhibit its expression.
Disease Class: Lung adenocarcinoma				[13]
Sensitive Disease	Lung adenocarcinoma [ICD-11: 2C25.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	SPC-A1 cells	Lung	Homo sapiens (Human)	CVCL_6955
Experiment for Molecule Alteration	qRT-PCR; Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay; Flow cytometric analysis
Mechanism Description	Upregulation of miR7 increases the sensitivity of LA cells to CDDP via induction of apoptosis by targeting Bcl-2.
Disease Class: Nasopharyngeal carcinoma				[14]
Sensitive Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	CNE2 cells	Nasopharynx	Homo sapiens (Human)	CVCL_6889
	CNE2/DDP cells	Nasopharynx	Homo sapiens (Human)	CVCL_6889
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay; Flow cytometry assay-directed annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) assay
Mechanism Description	microRNA-125b reverses the multidrug resistance of nasopharyngeal carcinoma cells via targeting of Bcl-2.
Disease Class: Gallbladder cancer				[15]
Sensitive Disease	Gallbladder cancer [ICD-11: 2C13.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR125b-5p/BCL2 signaling pathway		Regulation	hsa05206
In Vitro Model	GBC-SD cells	Gallbladder	Homo sapiens (Human)	CVCL_6903
	NOZ cells	Gallbladder	Homo sapiens (Human)	CVCL_3079
	HEK293 FT cells	Kidney	Homo sapiens (Human)	CVCL_6911
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay; Annexin V/PI Apoptosis Detection assay
Mechanism Description	miR125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer.
Disease Class: Osteosarcoma				[16], [17]
Sensitive Disease	Osteosarcoma [ICD-11: 2B51.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	p53/p38/MAPK signaling pathway		Regulation	hsa04010
In Vitro Model	MG63 cells	Bone marrow	Homo sapiens (Human)	CVCL_0426
	SAOS-2 cells	Bone marrow	Homo sapiens (Human)	CVCL_0548
	U2OS cells	Bone	Homo sapiens (Human)	CVCL_0042
	HOS cells	Bone	Homo sapiens (Human)	CVCL_0312
	3AB-OS CSC cells	Bone marrow	Homo sapiens (Human)	CVCL_LM95
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR; Western blot analysis
Experiment for Drug Resistance	Trypan blue assay; Flow cytometry assay; CCK8 assay
Mechanism Description	miR-29b-1 overexpression sensitized 3AB-OS cells to chemotherapeutic drug-induced apoptosis miR-29b-1 negatively regulated the expression of Bcl-2. Overexpression of miR-125b inhibited proliferation, migration, and invasion of OS cells and reduced the chemotherapy resistance of OS cells to cisplatin by targeting Bcl-2.
Disease Class: Breast cancer				[18]
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
In Vitro Model	Hs-578T cells	Breast	Homo sapiens (Human)	CVCL_0332
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Acid phosphatase assay
Mechanism Description	When delivered directly by transfection the STAT5B and Hsp90 expression levels were reduced, but response to anti-Hsp90 drugs was not augmented. However, cellular growth was reduced and cisplatin-induced apoptosis was (+). Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90 expression, had no apparent effects on proliferation, but cellular migration and invasion were reduced and sensitivity to anti-Hsp90 drugs was (+).
Disease Class: Glioma				[19]
Sensitive Disease	Glioma [ICD-11: 2A00.1]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	U251 cells	Brain	Homo sapiens (Human)	CVCL_0021
	U87 cells	Brain	Homo sapiens (Human)	CVCL_0022
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Bcl-2 was a direct target of miR 873, and miR 873 decreased the level of the Bcl-2 protein in cisplatin-resistant glioma cells. Notably, re-expression of Bcl-2 attenuated the function of miR 873 in cisplatin-resistant glioma cells and the sensitivity of the cells to cisplatin.
Disease Class: Non-small cell lung cancer				[20]
Sensitive Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	Sk-MES-1 cells	Lung	Homo sapiens (Human)	CVCL_0630
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Down-regulation of miR-21 inhibited growth, colony formation, antiapoptotic Bcl-2 expression and promoted proapoptotic Bax and caspase-9 expression in A549 cells treated with DDP. Upregulation of miR-21 promoted growth and colony formation in Sk-MES-1 cells treated with DDP. Furthermore, downregulation of miR-21 reduced growth of implanted tumors, suggesting that miR-21 inhibition could enhance the sensitivity of A549 cells to DDP in vivo. These data suggest an appropriate combination of DDP and miR-21 regulation might be a potential approach to lung cancer therapy. Combined DDP application with miR-21 downregulation for the treatment of lung cancer would help achieve effective treatment and reduce DDP side effects.
Disease Class: Gastric cancer				[21]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	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.
Disease Class: HPV-related endocervical adenocarcinoma				[22], [23]
Sensitive Disease	HPV-related endocervical adenocarcinoma [ICD-11: 2E67.1]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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. And 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.
Disease Class: Lung cancer				[22], [23]
Sensitive Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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. And 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.
Disease Class: Nasopharyngeal carcinoma				[24]
Sensitive Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	5-8F cells	Nasopharynx	Homo sapiens (Human)	CVCL_C528
	CNE2 cells	Nasopharynx	Homo sapiens (Human)	CVCL_6889
	C666-1 cells	Throat	Homo sapiens (Human)	CVCL_7949
	CNE1 cells	Throat	Homo sapiens (Human)	CVCL_6888
	HONE1 cells	Throat	Homo sapiens (Human)	CVCL_8706
	6-10B cells	Nasopharynx	Homo sapiens (Human)	CVCL_C529
	SUNE-1 cells	Nasopharynx	Homo sapiens (Human)	CVCL_6946
	HNE-2 cells	Nasopharynx	Homo sapiens (Human)	CVCL_FA07
In Vivo Model	SCID-Beige nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-29c repressed expression of anti-apoptotic factors, Mcl-1 and Bcl-2 in NPC tissues and cell lines, cause the resstance to Cisplatin.
Disease Class: Neuroblastoma				[25]
Sensitive Disease	Neuroblastoma [ICD-11: 2A00.11]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	Kelly cells	Adrenal	Homo sapiens (Human)	CVCL_2092
	Sk-N-AS cells	Adrenal	Homo sapiens (Human)	CVCL_1700
	SH-SY5Y cells	Abdomen	Homo sapiens (Human)	CVCL_0019
In Vivo Model	Orthotopic xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR-204 direct targeting of the 3' UTR of BCL2 and NTRk2 (TrkB). BCL2 has a critical role in ensuring the survival of early developing cell types, NTRk2 is also a well-established pro-survival oncogene in neuroblastoma, signalling the activation of the PI3k/AkT pathway, a significant mechanism of drug resistance in neuroblastoma. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro.
Disease Class: Gastric adenocarcinoma				[22]
Sensitive Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Gastric cancer				[26]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	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.
Disease Class: Gastric cancer				[27]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Mitochondrial signaling pathway		Activation	hsa04217
In Vitro Model	SGC7901 cells	Gastric	Homo sapiens (Human)	CVCL_0520
	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.

Cytarabine

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Leukemia				[28]
Sensitive Disease	Leukemia [ICD-11: 2B33.6]			Disease Info
Sensitive Drug	Cytarabine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	HL60 cells	Peripheral blood	Homo sapiens (Human)	CVCL_0002
	HL-60/Ara-C-resistant cells	Blood	Homo sapiens (Human)	CVCL_1736
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Bcl-2 was conWrmed as adirect miR-181a target by immunoblot analysis andreporter gene assays. knockdown of Bcl-2 mimicked theeVect of enforced miR-181a expression by reducing cellviability. In addition, the apoptosis pathway was activated by cytochrome C release and caspase 9/caspase 3 activationafter miR-181a overexpression. Down-regulation of miR-181a and upregulation of Bcl-2in leukaemia cells confer resistance to Ara-C-based ther-apy.

Daunorubicin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Leukemia				[29]
Sensitive Disease	Leukemia [ICD-11: 2B33.6]			Disease Info
Sensitive Drug	Daunorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	K562 cells	Blood	Homo sapiens (Human)	CVCL_0004
	K562/A02 cells	Blood	Homo sapiens (Human)	CVCL_0368
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Anti-apoptotic BCL-2 contributes to the survival and chemoresistance of quiescent leukemia CD34+ cells, leukemia cells with decreased miR-181a expression and elevated BCL-2 protein expression were more resistant to DNR than the control cells.

Docetaxel

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Prostate cancer				[30]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]			Disease Info
Resistant Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	DU-145 cells	Prostate	Homo sapiens (Human)	CVCL_0105
	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	22RV1 cells	Prostate	Homo sapiens (Human)	CVCL_1045
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Acid phosphatase assay
Mechanism Description	miR-34a regulates BCL-2 and may, in part, regulate response to docetaxel. miR-34a was significantly decreased in prostate cancer versus normal tissues; in biochemical recurrence versus non-recurrence tissue and in metastatic versus primary disease prostate tissue. We confirmed BCL-2 as a target of miR-34a, by manipulating miR-34a expression in our parent and docetaxel resistant cell lines and subsequently assessing BCL-2 levels. Specifically, upon inhibition of miR-34a in sensitive parent cells (PC3 and 22Rv1) we observed an increase in BCL-2 expression, whereas mimicking miR-34a expression in docetaxel-resistant cells (PC3RD and 22Rv1RD) resulted in decreased BCL-2 expression.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Breast cancer				[31]
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Docetaxel primarily acts in G2-M phase, whereas it has diminished activity in G1 phase. Increased miR-34a expression may therefore be able to inhibit docetaxel activity by arresting cells in G1 phase.
Disease Class: Gastric cancer				[26]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Docetaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	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

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Osteosarcoma				[32]
Resistant Disease	Osteosarcoma [ICD-11: 2B51.0]			Disease Info
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	SAOS-2 cells	Bone marrow	Homo sapiens (Human)	CVCL_0548
	U2OS cells	Bone	Homo sapiens (Human)	CVCL_0042
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Matrigel colony formation assay; Hoechst33342 staining assay
Mechanism Description	In chemoresistant SAOS-2 and U2OS osteosarcomas cells, miR-143 levels were significantly downregulated and accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate of ALDH1+CD133+ cells, and an increase in Matrigel colony formation ability. H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells. Forced miR-143 expression significantly reversed chemoresistance as well as downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS-resistant cells. Forced miR-143 expression significantly inhibited tumor growth in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is associated with poor prognosis of patients with osteosarcoma underlying chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1+CD133+ cells, activation of autophagy, and inhibition of cell death.
Disease Class: Breast cancer				[33]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Resistant Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	MCF-7/ADR cells	Breast	Homo sapiens (Human)	CVCL_1452
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-181a played an important role in chemosensitivity to adriamycin in MCF-7 and MCF-7/ADR cells via targeting Bcl-2.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Disease Class: Lung small cell carcinoma				[10]
Sensitive Disease	Lung small cell carcinoma [ICD-11: 2C25.2]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	16HBE cells	Lung	Homo sapiens (Human)	CVCL_0112
	H446 cells	Lung	Homo sapiens (Human)	CVCL_1562
	H69 cells	Lung	Homo sapiens (Human)	CVCL_8121
	H69AR cells	Lung	Homo sapiens (Human)	CVCL_3513
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay; RT-qPCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR216a. HOTTIP functioned as an oncogene in SCLC progression by binding miR216a and abrogating its tumor-suppressive function in this setting. HOTTIP also increased the expression of anti-apoptotic factor BCL-2, a target gene of miR216a, and jointly enhanced chemoresistance of SCLC by regulating BCL-2.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Gastric cancer				[34]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
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.
Disease Class: Glioma				[35]
Sensitive Disease	Glioma [ICD-11: 2A00.1]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT signaling pathway		Inhibition	hsa04151
	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	U251 cells	Brain	Homo sapiens (Human)	CVCL_0021
	U87-MG cells	Brain	Homo sapiens (Human)	CVCL_0022
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay; Flow cytometry assay
Mechanism Description	microRNA-127 silencing significantly affects cell growth and increases the sensitivity to adriamycin. microRNA-127 silencing arrests the cell cycle, potentiates adriamycin-induced apoptosis, and increases cellular Rh-123 uptake. microRNA-127 silencing down-regulates MDR1, MRP1, Runx2, Bcl-2, Survivin and ErbB4 expression while up-regulates p53 expression. microRNA-127 silencing inhibits AkT phosphorylation.
Disease Class: Breast cancer				[36]
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	c-Jun signaling pathway		Inhibition	hsa04210
In Vitro Model	MDA-MB-468 cells	Breast	Homo sapiens (Human)	CVCL_0419
Experiment for Molecule Alteration	Immunoblotting techniques assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	HA/CD44 activates c-Jun signaling which, in turn, stimulates miR-21 expression and function. These events lead to the production of an anti-apoptosis protein, Bcl-2 and upregulation of survival proteins (IAPs) and Doxorubicin chemoresistance in MDA-MB-468 cells. cells. Inhibition of c-Jun signaling or silencing miR-21 expression/function not only results in Bcl-2 downregulation, but also causes a reduction of survival protein expression and enhances chemosensitivity to Doxorubicin.
Disease Class: Gastric adenocarcinoma				[22]
Sensitive Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Lung cancer				[22]
Sensitive Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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.
Disease Class: Gastric cancer				[26]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	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.
Disease Class: Gastric cancer				[27]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Doxorubicin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Mitochondrial signaling pathway		Activation	hsa04217
In Vitro Model	SGC7901 cells	Gastric	Homo sapiens (Human)	CVCL_0520
	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

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Disease Class: Lung small cell carcinoma				[10]
Sensitive Disease	Lung small cell carcinoma [ICD-11: 2C25.2]			Disease Info
Sensitive Drug	Etoposide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	16HBE cells	Lung	Homo sapiens (Human)	CVCL_0112
	H446 cells	Lung	Homo sapiens (Human)	CVCL_1562
	H69 cells	Lung	Homo sapiens (Human)	CVCL_8121
	H69AR cells	Lung	Homo sapiens (Human)	CVCL_3513
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay; RT-qPCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR216a.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Neuroblastoma				[25]
Sensitive Disease	Neuroblastoma [ICD-11: 2A00.11]			Disease Info
Sensitive Drug	Etoposide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	Kelly cells	Adrenal	Homo sapiens (Human)	CVCL_2092
	Sk-N-AS cells	Adrenal	Homo sapiens (Human)	CVCL_1700
	SH-SY5Y cells	Abdomen	Homo sapiens (Human)	CVCL_0019
In Vivo Model	Orthotopic xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR-204 direct targeting of the 3' UTR of BCL2 and NTRk2 (TrkB). BCL2 has a critical role in ensuring the survival of early developing cell types, NTRk2 is also a well-established pro-survival oncogene in neuroblastoma, signalling the activation of the PI3k/AkT pathway, a significant mechanism of drug resistance in neuroblastoma. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro.
Disease Class: Gastric adenocarcinoma				[22]
Sensitive Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Sensitive Drug	Etoposide			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Lung cancer				[22]
Sensitive Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Sensitive Drug	Etoposide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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.
Disease Class: Gastric cancer				[27]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Etoposide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Mitochondrial signaling pathway		Activation	hsa04217
In Vitro Model	SGC7901 cells	Gastric	Homo sapiens (Human)	CVCL_0520
	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.

Fludarabine

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Chronic lymphocytic leukemia				[37]
Sensitive Disease	Chronic lymphocytic leukemia [ICD-11: 2A82.0]			Disease Info
Sensitive Drug	Fludarabine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	CLL B cells	Lymph	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181a and miR-181b directly inhibit the expression of BCL-2, MCL-1 and XIAP by binding to the target sequence, sensitizes CLL cells to fludarabine-induced apoptosis.

Fluorouracil

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Gastric cancer				[38]
Resistant Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Resistant Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Up-regulation
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.
Disease Class: Colorectal cancer				[39]
Resistant Disease	Colorectal cancer [ICD-11: 2B91.1]			Disease Info
Resistant Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell viability		Activation	hsa05200
In Vitro Model	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	HCT-8 cells	Colon	Homo sapiens (Human)	CVCL_2478
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	The overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance associated protein 1, P glycoprotein, serine/threonine protein kinase mTOR and apoptosis regulator Bcl2.
Disease Class: Colon cancer				[40]
Resistant Disease	Colon cancer [ICD-11: 2B90.1]			Disease Info
Resistant Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	RkO cells	Colon	Homo sapiens (Human)	CVCL_0504
In Vivo Model	SCID mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay; Flow cytometry assay
Mechanism Description	miR-206 downregulation modulates 5-FU resistance in HCT116 cells by upregulating Bcl-2.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Colorectal cancer				[41]
Sensitive Disease	Colorectal cancer [ICD-11: 2B91.1]			Disease Info
Sensitive Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	BCL2 signaling pathway		Regulation	hsa04210
	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
In Vitro Model	SW480 cells	Colon	Homo sapiens (Human)	CVCL_0546
	SW620 cells	Colon	Homo sapiens (Human)	CVCL_0547
	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	LOVO cells	Colon	Homo sapiens (Human)	CVCL_0399
	RkO cells	Colon	Homo sapiens (Human)	CVCL_0504
	HT-29 cells	Colon	Homo sapiens (Human)	CVCL_0320
	LS174T cells	Colon	Homo sapiens (Human)	CVCL_1384
	COLO205 cells	Colon	Homo sapiens (Human)	CVCL_F402
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	BCL2 is a direct target of miR-139-5p in colorectal cancer cells and showed that the tumour suppressor activity of miR-139-5p is mediated by the modulation of BCL2 expression. BCL2 family proteins regulate and contribute to programmed cell death or apoptosis. The cell apoptosis results showed the induction of apoptotic cells contributed greatly to 5-Fu and OXA drug sensitivity, which was consistent with the multidrug resistance mechanisms. miR-139-5p is downregulated in colorectal cancer cells and tissues, and its inhibitory effects on cell migration, invasion, and drug sensitivity are mediated by the downregulation of its target BCL2.
Disease Class: Gastric cancer				[34]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Down-regulation
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.
Disease Class: Colorectal cancer				[42]
Sensitive Disease	Colorectal cancer [ICD-11: 2B91.1]			Disease Info
Sensitive Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
In Vivo Model	CRC nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis; Immunofluorescence analysis
Experiment for Drug Resistance	WST assay
Mechanism Description	microRNA-129 (miR-129) trigger apoptosis by suppressing key anti-apoptotic protein, B-cell lymphoma 2 (BCL2), enhanced the cytotoxic effect of 5-fluorouracil both in vitro and in vivo.
Disease Class: Gastric cancer				[43]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Gastric adenocarcinoma				[22]
Sensitive Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Sensitive Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Lung cancer				[22]
Sensitive Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Sensitive Drug	Fluorouracil			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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.

Fulvestrant

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Breast cancer				[44]
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Sensitive Drug	Fulvestrant			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	PI3K/AKT/mTOR signaling pathway		Regulation	hsa04151
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
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-21 is a miRNA that is overexpressed in most tumor types, and acts as an oncogene by targeting many suppressor genes related to proliferation, apoptosis, and invasion. miR-21 facilitates tumor growth and invasion by targeting programmed cell death 4 (PDCD4), PTEN, and Bcl-2. silencing of miR-21 sensitized ER+ breast cancer cells to TAM and FUL induced cell apoptosis.

Gefitinib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Disease Class: Esophageal squamous cell carcinoma				[45]
Resistant Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.3]			Disease Info
Resistant Drug	Gefitinib			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell viability		Activation	hsa05200
	miR129/BCL2 signaling pathway		Regulation	hsa05206
In Vitro Model	TE-1 cells	Esophagus	Homo sapiens (Human)	CVCL_1759
	KYSE-450 cells	Esophagus	Homo sapiens (Human)	CVCL_1353
	TE6 cells	Esophageal	Homo sapiens (Human)	CVCL_1765
	TE8 cells	Esophageal	Homo sapiens (Human)	CVCL_1766
	TTn cells	Esophageal	Homo sapiens (Human)	CVCL_3175
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; TUNEL assay
Mechanism Description	Exosome-mediated transfer of PART1 promoted gefitinib resistance by competitively binding to miR-129 to facilitate Bcl-2 expression in ESCC cells.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Non-small cell lung cancer				[46]
Resistant Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Resistant Drug	Gefitinib			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell viability		Activation	hsa05200
In Vitro Model	PC9 cells	Lung	Homo sapiens (Human)	CVCL_B260
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Flow cytometry assay
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-214 level was upregulated in gefitinib-resistant PC-9GR cells and their derived exosomes while anti-apoptotic protein of bcl-2 is uoregulated.

Gemcitabine

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Pancreatic cancer				[47]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]			Disease Info
Resistant Drug	Gemcitabine			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Upregulation of Bcl-2 expression was detected in cells transfected with miR-21 mimics, accompanied by downregulated Bax expression, less apoptosis, lower caspase-3 activity, decreased chemosensitivity to gemcitabine and increased proliferation.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Malignant pleural mesothelioma				[48]
Sensitive Disease	Malignant pleural mesothelioma [ICD-11: 2C26.0]			Disease Info
Sensitive Drug	Gemcitabine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MET-5A cells	Lung	Homo sapiens (Human)	CVCL_3749
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay; Colony formation assay
Mechanism Description	Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.
Disease Class: Pancreatic ductal adenocarcinoma				[49]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]			Disease Info
Sensitive Drug	Gemcitabine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	BCL-2 facilitates cell survival against chemotherapy via the blockage of Bax/Bak-induced apoptosis, miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.
Disease Class: Gastric cancer				[26]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Gemcitabine			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	NCI-N87 cells	Gastric	Homo sapiens (Human)	CVCL_1603
	MkN-45 cells	Gastric	Homo sapiens (Human)	CVCL_0434
	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.

Imatinib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Gastrointestinal stromal tumor				[50]
Sensitive Disease	Gastrointestinal stromal tumor [ICD-11: 2B5B.0]			Disease Info
Sensitive Drug	Imatinib			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	GIST-T1 cells	Gastric	Homo sapiens (Human)	CVCL_4976
Experiment for Molecule Alteration	RT-qPCR; Western blot analysis
Experiment for Drug Resistance	MTT assay; Annexin V-FITC Apoptosis Detection assay
Mechanism Description	miRNA-21 sensitizes gastrointesti.l stromal tumors (GISTs) cells to Imatinib via targeting B-cell lymphoma 2 (Bcl-2), miRNA-21 suppressed Bcl-2 expression in GIST cells and could function as a potent tumor suppressor in GIST.
Disease Class: Chronic myeloid leukemia				[51]
Sensitive Disease	Chronic myeloid leukemia [ICD-11: 2A20.0]			Disease Info
Sensitive Drug	Imatinib			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	p53 signaling pathway		Regulation	hsa04115
In Vitro Model	K562 cells	Blood	Homo sapiens (Human)	CVCL_0004
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	BCL-2, MCL-1 and XIAP were the target genes of miR-130a. BCL-2, MCL-1, TCL-1 and XIAP protein levels were significantly higher in patients with drug-sensitive CML cells. Transfected miR-130a mimics significantly decreased the protein expression of BCL-1, MCL-1 and XIAP. Transfected miR-130a significantly increased the CML sensitivity to Gleevec.

Oxaliplatin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Colorectal cancer				[41]
Sensitive Disease	Colorectal cancer [ICD-11: 2B91.1]			Disease Info
Sensitive Drug	Oxaliplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	BCL2 signaling pathway		Regulation	hsa04210
	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
In Vitro Model	SW480 cells	Colon	Homo sapiens (Human)	CVCL_0546
	SW620 cells	Colon	Homo sapiens (Human)	CVCL_0547
	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	LOVO cells	Colon	Homo sapiens (Human)	CVCL_0399
	RkO cells	Colon	Homo sapiens (Human)	CVCL_0504
	HT-29 cells	Colon	Homo sapiens (Human)	CVCL_0320
	LS174T cells	Colon	Homo sapiens (Human)	CVCL_1384
	COLO205 cells	Colon	Homo sapiens (Human)	CVCL_F402
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	BCL2 is a direct target of miR-139-5p in colorectal cancer cells and showed that the tumour suppressor activity of miR-139-5p is mediated by the modulation of BCL2 expression. BCL2 family proteins regulate and contribute to programmed cell death or apoptosis. The cell apoptosis results showed the induction of apoptotic cells contributed greatly to 5-Fu and OXA drug sensitivity, which was consistent with the multidrug resistance mechanisms. miR-139-5p is downregulated in colorectal cancer cells and tissues, and its inhibitory effects on cell migration, invasion, and drug sensitivity are mediated by the downregulation of its target BCL2.
Disease Class: Gastric cancer				[34]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Oxaliplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
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.
Disease Class: Gastric cancer				[43]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Oxaliplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Colorectal carcinoma				[52]
Sensitive Disease	Colorectal carcinoma [ICD-11: 2B91.3]			Disease Info
Sensitive Drug	Oxaliplatin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	HCT-116/L-OHP cells	Kidney	Homo sapiens (Human)	CVCL_0291
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Elevated levels of miR-1915 in the mimics-transfected HCT116/L-OHP cells reduced Bcl-2 protein level and the luciferase activity of a Bcl-2 3'-untranslated region-based reporter, and also sensitized these cells to some anticancer drugs. miR-1915 could play a role in the development of MDR in colorectal carcinoma cells at least in part by modulation of apoptosis via targeting Bcl-2.

Paclitaxel

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Lung adenocarcinoma				[53]
Resistant Disease	Lung adenocarcinoma [ICD-11: 2C25.0]			Disease Info
Resistant Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Mitochondrial signaling pathway		Activation	hsa04217
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/Taxol cells	Lung	Homo sapiens (Human)	CVCL_W218
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Transwell Invasion assay
Mechanism Description	ANRIL, also known as CDkN2B antisense RNA1, was origi.lly identified in the familial melanoma patients, it is located within the CDkN2B-CDkN2A gene cluster at chromosome 9p21. ANRIL decreases Bcl-2 expression and increases PARP expression.
Disease Class: Lung adenocarcinoma				[53]
Resistant Disease	Lung adenocarcinoma [ICD-11: 2C25.0]			Disease Info
Resistant Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/Taxol cells	Lung	Homo sapiens (Human)	CVCL_W218
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Transwell Invasion assay
Mechanism Description	ANRIL functioning as a potential oncogene was up-regulated in LAD, and promoted the acquisition of chemo-resistance in paclitaxel partly through the mitochondrial pathway by modulating the expression of apoptosis-related protein cleaved-PARP and Bcl-2. ANRIL decreases Bcl-2 expression and increases PARP expression.
Disease Class: Breast cancer				[54]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Resistant Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
	MDA-MB-436 cells	Breast	Homo sapiens (Human)	CVCL_0623
	MDA-MB-435 cells	Breast	Homo sapiens (Human)	CVCL_0417
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Celltiter 96 aqueous one solution cell proliferation assay
Mechanism Description	miR-125b was up-regulated in Taxol-resistant cells, causing a marked inhibition of Taxol-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to Taxol in cancer cells. The pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) is a direct target of miR-125b. Down-regulation of Bak1 suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Non-small cell lung cancer				[55]
Sensitive Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Sensitive Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	H460 cells	Lung	Homo sapiens (Human)	CVCL_0459
	A549/PR cells	Lung	Homo sapiens (Human)	CVCL_0023
	H460/PR cells	Lung	Homo sapiens (Human)	CVCL_0459
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; Flow cytometric analysis
Mechanism Description	miR30a-5p increases paclitaxel sensitivity by promoting chemotherapy-induced apoptosis via downregulating BCL-2.
Disease Class: Breast cancer				[56]
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Sensitive Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
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
Mechanism Description	miR-21 inhibitors induced sensitivity of MCF-7/PR and SkBR-3/PR cells to paclitaxel. And miR-21 mimic can increase the expression of MDR1, Bcl-2/Bax and change cell morphology from parental cells to resistant cells.
Disease Class: Lung cancer				[57]
Sensitive Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Sensitive Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	PI3K/AKT/mTOR signaling pathway		Regulation	hsa04151
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	H1299 cells	Lung	Homo sapiens (Human)	CVCL_0060
	NCl-H596 cells	Lung	Homo sapiens (Human)	CVCL_1571
	NCI-H1734 cells	Lung	Homo sapiens (Human)	CVCL_1491
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-16 was also significantly downregulated in paclitaxel resistant lung cancer cells. anti-apoptotic protein Bcl-2 was directly targeted miR-16 in paclitaxel resistant lung cancer cells. the combined overexpression of miR-16 and miR-17 and subsequent paclitaxel treatment greatly sensitized paclitaxel resistant lung cancer cells to paclitaxel by inducing apoptosis via caspase-3 mediated pathway. Combined overexpression of miR-16 and miR-17 greatly reduced Beclin-1 and Bcl-2 expressions respectively. though miR-17 and miR-16 had no common target, both miR-16 and miR-17 jointly played roles in the development of paclitaxel resistance in lung cancer. miR-17 overexpression reduced cytoprotective autophagy by targeting Beclin-1, whereas overexpression of miR-16 potentiated paclitaxel induced apoptotic cell death by inhibiting anti-apoptotic protein Bcl-2.
Disease Class: Prostate cancer				[58]
Sensitive Disease	Prostate cancer [ICD-11: 2C82.0]			Disease Info
Sensitive Drug	Paclitaxel			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Trypan blue dye exclusion assay
Mechanism Description	SIRT1 plays crucial roles in various cellular processes including cell survival under genotoxic and oxidative stresses. Bcl2I is an anti-apoptotic factor. In PC3PR cells, reduced expression of miR-34a confers paclitaxel resistance via up-regulating SIRT1 and Bcl2 expression.

Pemetrexed

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Malignant pleural mesothelioma				[48]
Sensitive Disease	Malignant pleural mesothelioma [ICD-11: 2C26.0]			Disease Info
Sensitive Drug	Pemetrexed			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MET-5A cells	Lung	Homo sapiens (Human)	CVCL_3749
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay; Colony formation assay
Mechanism Description	Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine.

Sorafenib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Hepatocellular carcinoma				[59]
Sensitive Disease	Hepatocellular carcinoma [ICD-11: 2C12.2]			Disease Info
Sensitive Drug	Sorafenib			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	Huh-7 cells	Liver	Homo sapiens (Human)	CVCL_0336
	HL-7702 cells	Liver	Homo sapiens (Human)	CVCL_6926
	MHCC97-H cells	Liver	Homo sapiens (Human)	CVCL_4972
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	The restoration of miR-34a reduced cell viability, promoted cell apoptosis and potentiated sorafenib-induced apoptosis and toxicity in HCC cell lines by inhibiting Bcl-2 expression.

Stanozolol

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Disease Class: Hereditary angioedema			[60]
Resistant Disease	Hereditary angioedema [ICD-11: 4B05.0]		Disease Info
Resistant Drug	Stanozolol		Drug Info
Molecule Alteration	Expression	Up-regulation
Experimental Note	Discovered Using In-vivo Testing Model
In Vivo Model	Sprague Dawley male rats model		Rattus norvegicus
Experiment for Molecule Alteration	Gene expression analysis
Mechanism Description	Stanozolol can increases levels of Bax, Bcl-2, P53, caspase 3 and Bax/Bcl-2 ratio. Resistance training, 50 and 100 mg/kg Tribulus terrestris and resistance training along with Tribulus terrestris can decrease the Bax, Bcl-2, P53, caspase 3 and Bax/Bcl-2 ratio in rats exposed to Stanozolol.

Tamoxifen

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Breast cancer				[44]
Sensitive Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Sensitive Drug	Tamoxifen			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	PI3K/AKT/mTOR signaling pathway		Regulation	hsa04151
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
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-21 is a miRNA that is overexpressed in most tumor types, and acts as an oncogene by targeting many suppressor genes related to proliferation, apoptosis, and invasion. miR-21 facilitates tumor growth and invasion by targeting programmed cell death 4 (PDCD4), PTEN, and Bcl-2. silencing of miR-21 sensitized ER+ breast cancer cells to TAM and FUL induced cell apoptosis.

Temozolomide

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Glioma				[61]
Resistant Disease	Glioma [ICD-11: 2A00.1]			Disease Info
Resistant Drug	Temozolomide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	IGF1R/IRS1 signaling pathway		Activation	hsa04212
In Vitro Model	U251 cells	Brain	Homo sapiens (Human)	CVCL_0021
	U87 cells	Brain	Homo sapiens (Human)	CVCL_0022
	U138 cells	Brain	Homo sapiens (Human)	CVCL_0020
	HEK293 cells	Kidney	Homo sapiens (Human)	CVCL_0045
	NHA cells	Brain	Homo sapiens (Human)	N.A.
	LN382 cells	Brain	Homo sapiens (Human)	CVCL_3956
	SF295 cells	Brain	Homo sapiens (Human)	CVCL_1690
	SHG-44 cells	Brain	Homo sapiens (Human)	CVCL_6728
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Up-regulation of miR-497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl-2. The silencing of miR-497 decreased the protein levels of IGF1R/IRS1 pathway-related proteins, that is, IGF1R, IRS1, mTOR, and Bcl-2.
Disease Class: Glioma				[62]
Resistant Disease	Glioma [ICD-11: 2A00.1]			Disease Info
Resistant Drug	Temozolomide			Drug Info
Molecule Alteration	Expression		Down-regulation
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	A172 cells	Brain	Homo sapiens (Human)	CVCL_0131
In Vitro Model	U138-MG cells	Brain	Homo sapiens (Human)	CVCL_0020
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The mechanism responsible for resistance of glioma cells to temozolomide was associated with miR-16-mediated downregulation of Bcl-2. miR-16 may function as an important modifier of the response of glioma cells to temozolomide.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Glioma				[63]
Sensitive Disease	Glioma [ICD-11: 2A00.1]			Disease Info
Sensitive Drug	Temozolomide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	U251 cells	Brain	Homo sapiens (Human)	CVCL_0021
	U87MG cells	Brain	Homo sapiens (Human)	CVCL_GP63
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; Transwell assay
Mechanism Description	Upregulation of miR-181b-5p targets Bcl-2 directly and may function as an important modifier to sensitize glioma cells to TMZ.
Disease Class: Glioblastoma				[64]
Sensitive Disease	Glioblastoma [ICD-11: 2A00.02]			Disease Info
Sensitive Drug	Temozolomide			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	A172 cells	Brain	Homo sapiens (Human)	CVCL_0131
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	The chemoresistant cell survival mediated with Bcl-2 was inhibited by overexpression of miR-1271 and was enhanced by depletion of miR-1271.

Trastuzumab

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Breast cancer				[65]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Resistant Drug	Trastuzumab			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	BCL2/Bax apoptosis signaling pathway		Activation	hsa04210
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	BT474 cells	Breast	Homo sapiens (Human)	CVCL_0179
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Exosomal LncRNA-SNHG14 may induce trastuzumab resistance through inhibiting apoptotic proteins and cell apoptosis via Bcl-2/Bax pathway.

Venetoclax

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)			Click to Show/Hide
Disease Class: Lymphoma				[66]
Resistant Disease	Lymphoma [ICD-11: 2A90- 2A85]			Disease Info
Resistant Drug	Venetoclax			Drug Info
Molecule Alteration	Missense mutation		p.F104I (c.310T>A)
Experimental Note	Identified from the Human Clinical Data
Disease Class: Chronic lymphocytic leukemia				[67]
Resistant Disease	Chronic lymphocytic leukemia [ICD-11: 2A82.0]			Disease Info
Resistant Drug	Venetoclax			Drug Info
Molecule Alteration	Missense mutation		p.G101V (c.302G>T)
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	KMS-12-PE cells	Pleural effusion	Homo sapiens (Human)	CVCL_1333
Experiment for Drug Resistance	CellTiter-Glo assay; IC50 assay

Vincristine

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Gastric adenocarcinoma				[9]
Resistant Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Resistant Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Fas/FasL signaling pathway		Regulation	hsa04210
In Vitro Model	SGC7901 cells	Gastric	Homo sapiens (Human)	CVCL_0520
	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.
Disease Class: Lung cancer				[9]
Resistant Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Resistant Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Fas/FasL signaling pathway		Regulation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Colon cancer				[68]
Sensitive Disease	Colon cancer [ICD-11: 2B90.1]			Disease Info
Sensitive Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	HCT8 cells	Colon	Homo sapiens (Human)	CVCL_2478
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-15a and Mir-16 reverse drug resistance in colon cancer cells, possibly by down-regulating the expression of Bcl-2 protein.
Disease Class: HPV-related endocervical adenocarcinoma				[22], [23]
Sensitive Disease	HPV-related endocervical adenocarcinoma [ICD-11: 2E67.1]			Disease Info
Sensitive Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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. And 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.
Disease Class: Gastric adenocarcinoma				[22]
Sensitive Disease	Gastric adenocarcinoma [ICD-11: 2B72.0]			Disease Info
Sensitive Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Down-regulation
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
	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.
Disease Class: Lung cancer				[22]
Sensitive Disease	Lung cancer [ICD-11: 2C25.5]			Disease Info
Sensitive Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	A549/CDDP cells	Lung	Homo sapiens (Human)	CVCL_0023
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. And 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.
Disease Class: Gastric cancer				[27]
Sensitive Disease	Gastric cancer [ICD-11: 2B72.1]			Disease Info
Sensitive Drug	Vincristine			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Mitochondrial signaling pathway		Activation	hsa04217
In Vitro Model	SGC7901 cells	Gastric	Homo sapiens (Human)	CVCL_0520
	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.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

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Brain cancer [ICD-11: 2A00]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Nervous tissue
The Specified Disease	Brain cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.33E-53; Fold-change: -2.89E-01; Z-score: -1.09E+00
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
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The Studied Tissue	Brainstem tissue
The Specified Disease	Glioma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 6.38E-01; Fold-change: -2.32E-01; Z-score: -4.42E-01
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
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The Studied Tissue	White matter
The Specified Disease	Glioma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.61E-03; Fold-change: -1.06E+00; Z-score: -1.89E+00
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual
The Studied Tissue	Brainstem tissue
The Specified Disease	Neuroectodermal tumor
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.35E-04; Fold-change: -3.43E-01; Z-score: -2.10E+00
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
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Chronic myeloid leukemia [ICD-11: 2A20]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Whole blood
The Specified Disease	Myelofibrosis
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.81E-02; Fold-change: -9.42E-02; Z-score: -1.04E+00
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual
The Studied Tissue	Whole blood
The Specified Disease	Polycythemia vera
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 8.10E-01; Fold-change: -5.16E-03; Z-score: -5.58E-02
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Multiple myeloma [ICD-11: 2A83]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Bone marrow
The Specified Disease	Multiple myeloma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.64E-04; Fold-change: 4.26E-01; Z-score: 2.16E+00
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual
The Studied Tissue	Peripheral blood
The Specified Disease	Multiple myeloma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 6.24E-01; Fold-change: -9.91E-02; Z-score: -3.63E-01
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Lymphoma [ICD-11: 2A90- 2A85]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Tonsil tissue
The Specified Disease	Lymphoma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 6.81E-01; Fold-change: -1.00E-01; Z-score: -4.38E-01
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
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Esophageal cancer [ICD-11: 2B70]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Esophagus
The Specified Disease	Esophageal cancer
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 4.87E-01; Fold-change: -2.59E-03; Z-score: -1.05E-02
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue

Gastric cancer [ICD-11: 2B72]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Gastric tissue
The Specified Disease	Gastric cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 5.02E-02; Fold-change: -2.14E-01; Z-score: -2.16E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 8.23E-03; Fold-change: -1.92E-01; Z-score: -7.94E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Colon cancer [ICD-11: 2B90]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Colon
The Specified Disease	Colon cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 4.01E-51; Fold-change: -4.00E-01; Z-score: -1.75E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 1.49E-51; Fold-change: -4.90E-01; Z-score: -2.13E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Pancreatic cancer [ICD-11: 2C10]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Pancreas
The Specified Disease	Pancreatic cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.85E-02; Fold-change: -2.63E-01; Z-score: -8.16E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 4.14E-09; Fold-change: -2.43E-01; Z-score: -9.77E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Liver cancer [ICD-11: 2C12]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Liver
The Specified Disease	Liver cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.81E-06; Fold-change: -1.56E-01; Z-score: -7.15E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 3.33E-41; Fold-change: -3.42E-01; Z-score: -1.58E+00
The Expression Level of Disease Section Compare with the Other Disease Section	p-value: 1.09E-03; Fold-change: -4.98E-01; Z-score: -5.03E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals Molecule expression in tissue other than the diseased tissue of patients
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual Download Molecule expression data in the tissue of the other disease section

Lung cancer [ICD-11: 2C25]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Lung
The Specified Disease	Lung cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 9.45E-01; Fold-change: 1.35E-02; Z-score: 5.07E-02
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 2.56E-04; Fold-change: 7.58E-02; Z-score: 3.73E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Breast cancer [ICD-11: 2C60]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Breast tissue
The Specified Disease	Breast cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.08E-24; Fold-change: -2.26E-01; Z-score: -7.40E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 1.67E-01; Fold-change: -6.74E-02; Z-score: -1.91E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Ovarian cancer [ICD-11: 2C73]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Ovary
The Specified Disease	Ovarian cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 2.42E-03; Fold-change: -3.67E-01; Z-score: -1.36E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 6.19E-03; Fold-change: 3.84E-01; Z-score: 1.20E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Cervical cancer [ICD-11: 2C77]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Cervix uteri
The Specified Disease	Cervical cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 7.36E-01; Fold-change: 3.06E-02; Z-score: 1.66E-01
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Prostate cancer [ICD-11: 2C82]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Prostate
The Specified Disease	Prostate cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.29E-02; Fold-change: 1.57E-01; Z-score: 6.18E-01
Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Tissue-specific Molecule Abundances in Healthy Individuals

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Download the Tissue-Specific Variation(s) Profile

References

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Ref 23	miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol. 2012 Mar;29(1):384-91. doi: 10.1007/s12032-010-9797-4. Epub 2011 Jan 22.
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Ref 25	MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer. 2012 Sep 4;107(6):967-76. doi: 10.1038/bjc.2012.356. Epub 2012 Aug 14.
Ref 26	Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008 Sep 21;8:266. doi: 10.1186/1471-2407-8-266.
Ref 27	miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008 Jul 15;123(2):372-379. doi: 10.1002/ijc.23501.
Ref 28	miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis. J Cancer Res Clin Oncol. 2012 Apr;138(4):595-602. doi: 10.1007/s00432-011-1137-3. Epub 2012 Jan 1.
Ref 29	miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2. Acta Biochim Biophys Sin (Shanghai). 2012 Mar;44(3):269-77. doi: 10.1093/abbs/gmr128. Epub 2012 Jan 26.
Ref 30	miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression. Prostate. 2014 Sep;74(13):1320-34. doi: 10.1002/pros.22848. Epub 2014 Jul 22.
Ref 31	miRNA-34a is associated with docetaxel resistance in human breast cancer cells. Breast Cancer Res Treat. 2012 Jan;131(2):445-54. doi: 10.1007/s10549-011-1424-3. Epub 2011 Mar 12.
Ref 32	microRNA-143 is associated with the survival of ALDH1+CD133+ osteosarcoma cells and the chemoresistance of osteosarcoma. Exp Biol Med (Maywood). 2015 Jul;240(7):867-75. doi: 10.1177/1535370214563893. Epub 2015 Jan 8.
Ref 33	The function role of miR-181a in chemosensitivity to adriamycin by targeting Bcl-2 in low-invasive breast cancer cells. Cell Physiol Biochem. 2013;32(5):1225-37. doi: 10.1159/000354521. Epub 2013 Nov 14.
Ref 34	MiR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened. Int J Clin Exp Pathol. 2015 Jun 1;8(6):6397-406. eCollection 2015.
Ref 35	Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells. Int J Clin Exp Pathol. 2015 Jun 1;8(6):6107-16. eCollection 2015.
Ref 36	Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer. 2014 Mar 8;13:52. doi: 10.1186/1476-4598-13-52.
Ref 37	miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis. 2012 Jul;33(7):1294-301. doi: 10.1093/carcin/bgs179. Epub 2012 May 18.
Ref 38	LncRNA PVT1 Mediates Antiapoptosis and 5-Fluorouracil Resistance via Increasing Bcl2 Expression in Gastric Cancer. J Oncol. 2019 May 8;2019:9325407. doi: 10.1155/2019/9325407. eCollection 2019.
Ref 39	Knockdown of long non coding RNA PVT1 reverses multidrug resistance in colorectal cancer cells. Mol Med Rep. 2018 Jun;17(6):8309-8315. doi: 10.3892/mmr.2018.8907. Epub 2018 Apr 20.
Ref 40	miR-206 regulates 5-FU resistance by targeting Bcl-2 in colon cancer cells. Onco Targets Ther. 2018 Mar 29;11:1757-1765. doi: 10.2147/OTT.S159093. eCollection 2018.
Ref 41	miR-139-5p Inhibits the Epithelial-Mesenchymal Transition and Enhances the Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating BCL2. Sci Rep. 2016 May 31;6:27157. doi: 10.1038/srep27157.
Ref 42	miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer. Cell Death Dis. 2013 Jun 6;4(6):e659. doi: 10.1038/cddis.2013.193.
Ref 43	miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis. 2012 Nov 15;3(11):e423. doi: 10.1038/cddis.2012.160.
Ref 44	Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells. Biomed Pharmacother. 2016 Feb;77:37-44. doi: 10.1016/j.biopha.2015.11.005. Epub 2015 Dec 12.
Ref 45	Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA. J Exp Clin Cancer Res. 2018 Jul 27;37(1):171. doi: 10.1186/s13046-018-0845-9.
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Ref 49	miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2. Oncol Rep. 2013 May;29(5):1769-76. doi: 10.3892/or.2013.2297. Epub 2013 Feb 21.
Ref 50	miRNA-21 sensitizes gastrointestinal stromal tumors (GISTs) cells to Imatinib via targeting B-cell lymphoma 2 (Bcl-2). Eur Rev Med Pharmacol Sci. 2016 Sep;20(17):3574-81.
Ref 51	Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia. Cancer Gene Ther. 2015 Dec;22(12):573-80. doi: 10.1038/cgt.2015.50. Epub 2015 Oct 23.
Ref 52	miR-1915 inhibits Bcl-2 to modulate multidrug resistance by increasing drug-sensitivity in human colorectal carcinoma cells. Mol Carcinog. 2013 Jan;52(1):70-8. doi: 10.1002/mc.21832. Epub 2011 Nov 28.
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Ref 56	[Effects of miRNA-21 on paclitaxel-resistance in human breast cancer cells]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2015 Jul;44(4):400-9. doi: 10.3785/j.issn.1008-9292.2015.07.09.
Ref 57	MiR-16 targets Bcl-2 in paclitaxel-resistant lung cancer cells and overexpression of miR-16 along with miR-17 causes unprecedented sensitivity by simultaneously modulating autophagy and apoptosis. Cell Signal. 2015 Feb;27(2):189-203. doi: 10.1016/j.cellsig.2014.11.023. Epub 2014 Nov 27.
Ref 58	MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate. 2010 Oct 1;70(14):1501-12. doi: 10.1002/pros.21185.
Ref 59	MicroRNA-34a targets Bcl-2 and sensitizes human hepatocellular carcinoma cells to sorafenib treatment. Technol Cancer Res Treat. 2014 Feb;13(1):77-86. doi: 10.7785/tcrt.2012.500364. Epub 2013 Jul 11.
Ref 60	Anti-Apoptotic Effects of Resistance Training and Tribulus Terrestris Consumption in the Heart Tissue of Rats Exposed to Stanozolol .Eurasian J Med. 2021 Jun;53(2):79-84. doi: 10.5152/eurasianjmed.2021.20051. 10.5152/eurasianjmed.2021.20051
Ref 61	Up-regulation of miR-497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl-2. Cancer Med. 2017 Feb;6(2):452-462. doi: 10.1002/cam4.987. Epub 2017 Jan 8.
Ref 62	MiR-16 modulate temozolomide resistance by regulating BCL-2 in human glioma cells. Int J Clin Exp Pathol. 2015 Oct 1;8(10):12698-707. eCollection 2015.
Ref 63	MiR-181b-5p modulates chemosensitivity of glioma cells to temozolomide by targeting Bcl-2. Biomed Pharmacother. 2019 Jan;109:2192-2202. doi: 10.1016/j.biopha.2018.11.074. Epub 2018 Nov 27.
Ref 64	Chemo-resistance of A172 glioblastoma cells is controlled by miR-1271-regulated Bcl-2. Biomed Pharmacother. 2018 Dec;108:734-740. doi: 10.1016/j.biopha.2018.08.102. Epub 2018 Sep 21.
Ref 65	Exosome-mediated transfer of lncRNA SNHG14 promotes trastuzumab chemoresistance in breast cancer. Int J Oncol. 2018 Sep;53(3):1013-1026. doi: 10.3892/ijo.2018.4467. Epub 2018 Jul 3.
Ref 66	Characterization of a novel venetoclax resistance mutation (BCL2 Phe104Ile) observed in follicular lymphomaBr J Haematol. 2019 Sep;186(6):e188-e191. doi: 10.1111/bjh.16069. Epub 2019 Jun 24.
Ref 67	Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutationsNat Commun. 2019 Jun 3;10(1):2385. doi: 10.1038/s41467-019-10363-1.
Ref 68	[miR-15a and miR-16 modulate drug resistance by targeting bcl-2 in human colon cancer cells]. Zhonghua Zhong Liu Za Zhi. 2014 Dec;36(12):897-902.

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Prof. Feng ZHU (zhufeng@zju.edu.cn)