Disease Information

General Information of the Disease (ID: DIS00069)

• Name: Oral squamous cell carcinoma
• ICD: ICD-11: 2B6E

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  MRAP: Metabolic Reprogramming via Altered Pathways

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 10 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Resistant Disease: Oral cancer [ICD-11: 2B6E.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.32E-01; Fold-change: 5.64E-02; Z-score: 1.54E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: UM-SCC-1 cells; Ovary; Homo sapiens (Human); CVCL_7707
• In Vitro Model: WSU-HN30 cells; Pleural effusion; Homo sapiens (Human); CVCL_5525
• In Vitro Model: WSU-HN6 cells; Urinary bladder; Homo sapiens (Human); CVCL_5516
• Experiment for Molecule Alteration: qRT-PCR; Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: E-cigarette aerosol exposure alters the expression of drug influx and efflux transporters.Among the other drug efflux ATPase genes previously reported to contribute to cisplatin resistance ABCG2, ABCC2, ABCA1, and ABCC1 were significantly up-regulated in at least one cell line.

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [3]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.17E-05; Fold-change: 1.19E-01; Z-score: 4.53E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Caspase-3 signaling pathway; Activation; hsa04210
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: OSCC3 cells; Tongue; Homo sapiens (Human); CVCL_L894
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of LncRNA ANRIL in tumour cells. ANRIL knockdown overcomes Mk-induced cisplatin resistance via activation of caspase-3-dependent apoptosis. Overexpression of LncRNA ANRIL promots the up-regulation of ABC family proteins MRP1 and ABCC2, which ultimately results in tumour cell resistance to cisplatin.

Key Molecule: ATP-binding cassette sub-family C2 (ABCC2) [3]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Caspase-3 signaling pathway; Activation; hsa04210
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: OSCC3 cells; Tongue; Homo sapiens (Human); CVCL_L894
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of LncRNA ANRIL in tumour cells. ANRIL knockdown overcomes Mk-induced cisplatin resistance via activation of caspase-3-dependent apoptosis. Overexpression of LncRNA ANRIL promots the up-regulation of ABC family proteins MRP1 and ABCC2, which ultimately results in tumour cell resistance to cisplatin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PP2A B subunit isoform R5-alpha (PPP2R5A) [5]

• Resistant Disease: Oral cancer [ICD-11: 2B6E.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.94E-07; Fold-change: -7.78E-02; Z-score: -6.15E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PPP2R5A/Wnt signaling pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: MDA-1386Ln cells; Tongue; Homo sapiens (Human); CVCL_H541
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vitro Model: UM1 cells; Tongue; Homo sapiens (Human); CVCL_VH00
• In Vitro Model: UM2 cells; Tongue; Homo sapiens (Human); CVCL_VH01
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis; Dual luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: microRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway. Suppression of miR218 or PPP2R5A significantly promoted or reduced cisplatin-induced apoptosis, respectively. PPP2R5A overexpression or beta-catenin knockdown inhibited miR218-mediated Wnt activation and partially restored cell sensitivity.

Key Molecule: GRB2-related adapter protein (GRAP) [10]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK/RAS signaling pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR654-5p targets GRAP to promote proliferation, metastasis, and chemoresistance of oral squamous cell carcinoma through Ras/MAPk signaling.

Key Molecule: Steroidogenic factor 1 (STF1) [11]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell adhesion; Activation; hsa04514
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: NHOk cells; Tongue; Homo sapiens (Human); N.A.
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: TSCCA cells; Tongue; Homo sapiens (Human); CVCL_VL15
• 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; Caspase-3 activity analysis
• Mechanism Description: UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR-184 in OSCC cells. UCA1 promoted the expression of SF1 by sponging miR-184 in CDDP-resistant OSCC cells.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-654-5p [10]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK/RAS signaling pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR654-5p targets GRAP to promote proliferation, metastasis, and chemoresistance of oral squamous cell carcinoma through Ras/MAPk signaling.

Key Molecule: CDKN2B antisense RNA 1 (CDKN2B-AS1) [3]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Caspase-3 signaling pathway; Activation; hsa04210
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: OSCC3 cells; Tongue; Homo sapiens (Human); CVCL_L894
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of LncRNA ANRIL in tumour cells. ANRIL knockdown overcomes Mk-induced cisplatin resistance via activation of caspase-3-dependent apoptosis. Overexpression of LncRNA ANRIL promots the up-regulation of ABC family proteins MRP1 and ABCC2, which ultimately results in tumour cell resistance to cisplatin.

Key Molecule: hsa-miR-184 [11]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: NHOk cells; Tongue; Homo sapiens (Human); N.A.
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: TSCCA cells; Tongue; Homo sapiens (Human); CVCL_VL15
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR; Dual luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Caspase-3 activity analysis
• Mechanism Description: LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

Key Molecule: Urothelial cancer associated 1 (UCA1) [11]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: NHOk cells; Tongue; Homo sapiens (Human); N.A.
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: TSCCA cells; Tongue; Homo sapiens (Human); CVCL_VL15
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Caspase-3 activity analysis
• Mechanism Description: LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

Key Molecule: hsa-mir-218 [5]

• Resistant Disease: Oral cancer [ICD-11: 2B6E.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PPP2R5A/Wnt signaling pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: MDA-1386Ln cells; Tongue; Homo sapiens (Human); CVCL_H541
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vitro Model: UM1 cells; Tongue; Homo sapiens (Human); CVCL_VH00
• In Vitro Model: UM2 cells; Tongue; Homo sapiens (Human); CVCL_VH01
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: microRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway. Suppression of miR218 or PPP2R5A significantly promoted or reduced cisplatin-induced apoptosis, respectively. PPP2R5A overexpression or beta-catenin knockdown inhibited miR218-mediated Wnt activation and partially restored cell sensitivity.

Key Molecule: Long noncoding RNA lnc-IL7R (Lnc-IL7R) [12]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: OSCC3 cells; Tongue; Homo sapiens (Human); CVCL_L894
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: HIOEC-B cells; Tongue; Homo sapiens (Human); CVCL_6E44
• In Vitro Model: SCC-14a cells; Tongue; Homo sapiens (Human); CVCL_7719
• In Vitro Model: SCC-14b cells; Tongue; Homo sapiens (Human); CVCL_7720
• In Vitro Model: SCC1 cells; Tongue; Homo sapiens (Human); CVCL_A5SA
• Experiment for Molecule Alteration: Q-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TLR3 negatively manipulated the inflammation-related long noncoding RNA lnc-IL7R, knockdown of lnc-IL7R improved the chemotherapy sensitivity.

Key Molecule: Toll-like receptor 3 (TLR3) [12]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: OSCC3 cells; Tongue; Homo sapiens (Human); CVCL_L894
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: HIOEC-B cells; Tongue; Homo sapiens (Human); CVCL_6E44
• In Vitro Model: SCC-14a cells; Tongue; Homo sapiens (Human); CVCL_7719
• In Vitro Model: SCC-14b cells; Tongue; Homo sapiens (Human); CVCL_7720
• In Vitro Model: SCC1 cells; Tongue; Homo sapiens (Human); CVCL_A5SA
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TLR3 negatively manipulated the inflammation-related long noncoding RNA lnc-IL7R, knockdown of lnc-IL7R improved the chemotherapy sensitivity.

Key Molecule: hsa-mir-29a [13]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-29a expression was decreased in clinical OSCC cancer specimens. miR-29a negatively regulated MMP2 transcription and translation through directly binding to 3'-UTR. miR-29a overexpression could inhibit OSCC cancer cell invasion and anti-apoptotic ability, and vice versa.

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: phosphoinositide-3-dependent protein kinase 1 (PDPK1) [14]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• In Vitro Model: TW2.6 cells; Mouth; Homo sapiens (Human); CVCL_GZ05
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Immunohistochemical analysis revealed that higher PDK1 expression is associated with a poor prognosis in OSCC. The immunoprecipitation assay indicated PDK1/CD47 binding. PDK1 ligation significantly impaired OSCC orosphere formation and downregulated Sox2, Oct4, and CD133 expression. The combination of BX795 and cisplatin markedly reduced in OSCC cell's epithelial-mesenchymal transition, implying its synergistic effect. p-PDK1, CD47, Akt, PFKP, PDK3 and LDHA protein expression were significantly reduced, with the strongest inhibition in the combination group. Chemo/radiotherapy together with abrogation of PDK1 inhibits the oncogenic (Akt/CD47) and glycolytic (LDHA/PFKP/PDK3) signaling and, enhanced or sensitizes OSCC to the anticancer drug effect through inducing apoptosis and DNA damage together with metabolic reprogramming.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Collagenase 72 kDa type IV collagenase (MMP2) [13]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-29a expression was decreased in clinical OSCC cancer specimens. miR-29a negatively regulated MMP2 transcription and translation through directly binding to 3'-UTR. miR-29a overexpression could inhibit OSCC cancer cell invasion and anti-apoptotic ability, and vice versa.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-27b [15]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: FZD7/beta-catenin signaling pathway; Activation; hsa05224
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Colony formation assay; Flow cytometry assay
• Mechanism Description: miR-27b can increase the sensitivity of OSCC cells to cisplatin drugs, significantly inhibit OSCC cell proliferation, promote cell apoptosis, and inhibit cell invasion and migration, which may be related to the inhibition of FDZ7/beta-catenin signaling pathway by miR-27b.

Key Molecule: HOX transcript antisense RNA (HOTAIR) [16]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Key Molecule: hsa-let-7c [17]

• Sensitive Disease: Oral cancer [ICD-11: 2B6E.1]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: GNM cells; Oral; Homo sapiens (Human); CVCL_WL58
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The inhibitory effect of let-7c on various stemness phenotypes was reverted by IL-8, indicating that lower expression of let-7c may confer higher cancer stemness through a failure to downregulate IL-8.

Key Molecule: hsa-mir-222 [18]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: UM1 cells; Tongue; Homo sapiens (Human); CVCL_VH00
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Antisense (As)-miR-222 inhibits the expression of miR-222. In contrast, PUMA was dramaticallyup-regulated. IC50 values were significantly decreased in cells treated with As-miR-222 combined with CDDP, to a greater extent than in cells treated with CDDP alone. Furthermore, As-miR-222 (+) apoptosis and inhibited the invasiveness of UM1 cells. Analysis of the above data suggested that, in UM1 cells, there might be a regulatory loop between miR-222 and PUMA, and that miR-222 inhibition increased the chemosensitivity to CDDP.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Cadherin-1 (CDH1) [19]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HULC-depleted cells showed decreased expression of vimentin and N-cadherin and increased expression of E-cadherin, which shows that HULC participates in the EMT process and affects the expression levels of proteins that are crucial for cell proliferation and invasion.

Key Molecule: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [19]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HULC-depleted cells showed decreased expression of vimentin and N-cadherin and increased expression of E-cadherin, which shows that HULC participates in the EMT process and affects the expression levels of proteins that are crucial for cell proliferation and invasion.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [16]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Key Molecule: Ubiquitin-like-conjugating enzyme ATG3 (ATG3) [16]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Key Molecule: Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) [16]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Key Molecule: Beclin-1 (BECN1) [16]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Key Molecule: Autophagy-related protein LC3 B (MAP1LC3B) [16]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Key Molecule: Interleukin-8 (IL8) [17]

• Sensitive Disease: Oral cancer [ICD-11: 2B6E.1]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: GNM cells; Oral; Homo sapiens (Human); CVCL_WL58
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The inhibitory effect of let-7c on various stemness phenotypes was reverted by IL-8, indicating that lower expression of let-7c may confer higher cancer stemness through a failure to downregulate IL-8.

Key Molecule: Bcl-2-binding component 3 (BBC3) [18]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: UM1 cells; Tongue; Homo sapiens (Human); CVCL_VH00
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Antisense (As)-miR-222 inhibits the expression of miR-222. In contrast, PUMA was dramaticallyup-regulated. IC50 values were significantly decreased in cells treated with As-miR-222 combined with CDDP, to a greater extent than in cells treated with CDDP alone. Furthermore, As-miR-222 (+) apoptosis and inhibited the invasiveness of UM1 cells. Analysis of the above data suggested that, in UM1 cells, there might be a regulatory loop between miR-222 and PUMA, and that miR-222 inhibition increased the chemosensitivity to CDDP.

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Metalloproteinase inhibitor 3 (TIMP3) [2]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.62E-01; Fold-change: 5.13E-02; Z-score: 1.43E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: Annexin V-fluorescein isothiocyanate (FITC)/Hoechst double staining; MTT assay
• Mechanism Description: OSCC cells are resistant to doxorubicin through upregulation of miR221, which in turn downregulates TIMP3.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-221 [2]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Annexin V-fluorescein isothiocyanate (FITC)/Hoechst double staining; MTT assay
• Mechanism Description: OSCC cells are resistant to doxorubicin through upregulation of miR221, which in turn downregulates TIMP3.

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [4]

• Sensitive Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.68E-03; Fold-change: -3.93E-02; Z-score: -3.14E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The continuous administration of low dose 5FU with Taxol significantly inhibited the tumor growth. The treatment overcomes drug resistance in tumors by down-regulating multi-drug resistance transporter protein.

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: ETS homologous factor (EHF) [6]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.86E-05; Fold-change: -1.81E-01; Z-score: -4.92E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Beta5-integrin/c-Met signaling pathway; Inhibition; hsa01521
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: C9-IV3 cells; Oral; Homo sapiens (Human); N.A.
• In Vitro Model: CGHNC9 cells; Oral; Homo sapiens (Human); N.A.
• In Vitro Model: OC-3 cells; Oral; Homo sapiens (Human); CVCL_WL09
• In Vivo Model: CB17-SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-365-3p targets EHF to inhibit OSCC migration, invasion, and metastasis through kRT16.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-365a-3p [6]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Beta5-integrin/c-Met signaling pathway; Inhibition; hsa01521
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: C9-IV3 cells; Oral; Homo sapiens (Human); N.A.
• In Vitro Model: CGHNC9 cells; Oral; Homo sapiens (Human); N.A.
• In Vitro Model: OC-3 cells; Oral; Homo sapiens (Human); CVCL_WL09
• In Vivo Model: CB17-SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-365-3p targets EHF to inhibit OSCC migration, invasion, and metastasis through kRT16.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-654-5p [10]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK/RAS signaling pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR654-5p targets GRAP to promote proliferation, metastasis, and chemoresistance of oral squamous cell carcinoma through Ras/MAPk signaling.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GRB2-related adapter protein (GRAP) [10]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK/RAS signaling pathway; Regulation; N.A.
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR654-5p targets GRAP to promote proliferation, metastasis, and chemoresistance of oral squamous cell carcinoma through Ras/MAPk signaling.

Cetuximab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa_circ_0005379 [9]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cetuximab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vivo Model: Balb/c athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Upregualtion of hsa_circ_0005379 enhances the sensitivity of OSCC to anticancer drug cetuximab.

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [20]

• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [21]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Docetaxel
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [21]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Palbociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [21]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Palbociclib
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Vinblastine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [20]

• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Resistant Drug: Vinblastine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [8]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Ubc7
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: KBV20 cells were highly resistant to Vincristine

Key Molecule: Multidrug resistance protein 1 (ABCB1) [8]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Ubc6
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microscopic assay
• Mechanism Description: KBV20 cells were highly resistant to Vincristine

Clinical Trial Drug(s) 3 drug(s) in total

Anlotinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Methyltransferase like 1 (METTL1) [22]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Anlotinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Adding to this, our research shows that METTL1-modified m7G tRNA increases translation of enzymes associated with the respiratory chain, boosting OXPHOS capacity in anlotinib-resistant cells. This highlights the potential of epigenetic interventions in overcoming TKI resistance.

Key Molecule: Methyltransferase like 1 (METTL1) [22]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Anlotinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Adding to this, our research shows that METTL1-modified m8G tRNA increases translation of enzymes associated with the respiratory chain, boosting OXPHOS capacity in anlotinib-resistant cells. This highlights the potential of epigenetic interventions in overcoming TKI resistance.

Bafetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [21]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Bafetinib
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Perifosine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [8]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Perifosine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Perifosine increased cytotoxicity in P-gp-overexpressing drug-resistant KBV20C cancer cells

Key Molecule: Multidrug resistance protein 1 (ABCB1) [8]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Perifosine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microscopic assay
• Mechanism Description: Perifosine increased cytotoxicity in P-gp-overexpressing drug-resistant KBV20C cancer cells

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

Imexon

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [21]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Imexon
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

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

Cevipabulin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [20]

• Resistant Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Resistant Drug: Cevipabulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• In Vitro Model: KB-V1 cells; Mouth; Homo sapiens (Human); CVCL_2089
• In Vivo Model: Athymic nu/nu female mice xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Investigative Drug(s) 5 drug(s) in total

BX795

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: phosphoinositide-3-dependent protein kinase 1 (PDPK1) [14]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: BX795
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• In Vitro Model: TW2.6 cells; Mouth; Homo sapiens (Human); CVCL_GZ05
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Immunohistochemical analysis revealed that higher PDK1 expression is associated with a poor prognosis in OSCC. The immunoprecipitation assay indicated PDK1/CD47 binding. PDK1 ligation significantly impaired OSCC orosphere formation and downregulated Sox2, Oct4, and CD133 expression. The combination of BX795 and cisplatin markedly reduced in OSCC cell's epithelial-mesenchymal transition, implying its synergistic effect. p-PDK1, CD47, Akt, PFKP, PDK3 and LDHA protein expression were significantly reduced, with the strongest inhibition in the combination group. Chemo/radiotherapy together with abrogation of PDK1 inhibits the oncogenic (Akt/CD47) and glycolytic (LDHA/PFKP/PDK3) signaling and, enhanced or sensitizes OSCC to the anticancer drug effect through inducing apoptosis and DNA damage together with metabolic reprogramming.

Isoarnebin 4

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: BCL2 associated X protein (BAX) [23]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Isoarnebin 4
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Apoptosis signaling pathway; Activation; hsa04210
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: H357 cells; Oral; Homo sapiens (Human); CVCL_2462
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• Experiment for Molecule Alteration: Reactive oxygen species measurement assay; Mitochondrial membrane potential measurement assay; CD spectroscopy assay; DNA interaction assay; qRT-PCR; Western blot assay
• Experiment for Drug Resistance: Drug release assay; Cell viability assay; Morphological assay; Clonogenic assay; Tumor spheres assay; Annexin V-FITC/PI staining assay; Antimigratory assay
• Mechanism Description: Our study revealed the release time and anticancer potential of Shk on the SCC9 and H357 oral cancer cell lines. We investigated the antiproliferative, antimigratory, cell cycle arresting and apoptosis promoting activity of Shk in oral cancer cells by performing MTT and morphological assay, colony, and tumor sphere formation assay, AO/EtBr and DAPI staining, Annexin V-FITC/PI staining, assay for reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) measurement, comet assay, qRT-PCR, and western blot analysis. We also checked the interaction of DNA and Shk by docking and CD spectroscopy and EtBr displacement assay. As a result, we found that Shk reduced the viability, proliferation, and tumorigenicity of SCC9 and H357 cells in a time and concentration-dependent manner. We obtained half-maximal inhibitory concentration (IC50) at 0.5 uM for SCC9 and 1.25 uM for H357. It promotes apoptosis via overexpressing proapoptotic Bax and caspase 3 via enhancing ROS that leads to MMP depletion and DNA damage and arrests cells at the G2/M & G2/S phase. The antimigratory activity of Shk was performed by analyzing the expression of markers of epithelial-mesenchymal transition like E-cadherin, ZO-1, N-cadherin, and vimentin. These overall results recommended that Shk shows potent anticancer activity against oral cancer cell lines in both in vitro and ex vivo conditions. So, it could be an excellent agent for the treatment of oral cancer.

Key Molecule: Caspase-3 (CASP3) [23]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Isoarnebin 4
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Apoptosis signaling pathway; Activation; hsa04210
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: H357 cells; Oral; Homo sapiens (Human); CVCL_2462
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• Experiment for Molecule Alteration: Reactive oxygen species measurement assay; Mitochondrial membrane potential measurement assay; CD spectroscopy assay; DNA interaction assay; qRT-PCR; Western blot assay
• Experiment for Drug Resistance: Drug release assay; Cell viability assay; Morphological assay; Clonogenic assay; Tumor spheres assay; Annexin V-FITC/PI staining assay; Antimigratory assay
• Mechanism Description: Our study revealed the release time and anticancer potential of Shk on the SCC9 and H357 oral cancer cell lines. We investigated the antiproliferative, antimigratory, cell cycle arresting and apoptosis promoting activity of Shk in oral cancer cells by performing MTT and morphological assay, colony, and tumor sphere formation assay, AO/EtBr and DAPI staining, Annexin V-FITC/PI staining, assay for reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) measurement, comet assay, qRT-PCR, and western blot analysis. We also checked the interaction of DNA and Shk by docking and CD spectroscopy and EtBr displacement assay. As a result, we found that Shk reduced the viability, proliferation, and tumorigenicity of SCC9 and H357 cells in a time and concentration-dependent manner. We obtained half-maximal inhibitory concentration (IC50) at 0.5 uM for SCC9 and 1.25 uM for H357. It promotes apoptosis via overexpressing proapoptotic Bax and caspase 3 via enhancing ROS that leads to MMP depletion and DNA damage and arrests cells at the G2/M & G2/S phase. The antimigratory activity of Shk was performed by analyzing the expression of markers of epithelial-mesenchymal transition like E-cadherin, ZO-1, N-cadherin, and vimentin. These overall results recommended that Shk shows potent anticancer activity against oral cancer cell lines in both in vitro and ex vivo conditions. So, it could be an excellent agent for the treatment of oral cancer.

Isoliquiritigenin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Threonine 34 phosphorylation (Thr34) [24]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Isoliquiritigenin
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Akt-Wee1-CDK1 signaling pathway; Regulation; N.A.
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC-4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: CCD-118Sk cells; N.A.; Homo sapiens (Human); CVCL_Y116
• In Vivo Model: Athymic female nude mice; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay; Ubiquitination assay; Akt kinase activity assay; Immunohistochemistry
• Experiment for Drug Resistance: MTS assay; Soft agar assay; Plate colony formation assay; In vivo tumor growth assay; Blood assay
• Mechanism Description: Here, we found that ISL inhibited the viability and colony formation of OSCC, and promoted their apoptosis. The immunoblotting data showed that ISL treatment significantly decreased survivin expression. Mechanistically, ISL suppressed survivin phosphorylation on Thr34 by deregulating Akt-Wee1-CDK1 signaling, which facilitated survivin for ubiquitination degradation. ISL inhibited CAL27 tumor growth and decreased p-Akt and survivin expression in vivo. Meanwhile, survivin overexpression caused cisplatin resistance of OSCC cells. ISL alone or combined with cisplatin overcame chemoresistance in OSCC cells. Overall, our results revealed that ISL exerted potent inhibitory effects via inducing Akt-dependent survivin ubiquitination in OSCC cells.

Cisplatinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [21]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatinum
• Molecule Alteration: Lactylation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: OSCC samples; Homo Sapiens
• Mechanism Description: We found that histone Kla-induced BCAM was overexpressed in OSCC, and a high BCAM level was related to a lower immune cell score and inhibition of immune response. On the other hand, BCAM induced EMT and angiogenesis, leading to OSCC malignant progression via activating the Notch signaling pathway. However, the difference of the BCAM function in Pan-cancers might be attributed to tumor heterogeneity. Taken together, BCAM played a vital role in OSCC chemotherapy resistance and prognosis and contributed to inhibition of the immune process, suggesting that it might be a novel therapeutic target for OSCC.

Succinate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Maternally expressed 3 (MEG3) [25]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Succinate
• Molecule Alteration: .; Expression
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: OLP type I keratinocytes; N.A.; N.A.; N.A.
• Experiment for Drug Resistance: Cell Titer-Glo assay; IC50 assay
• Mechanism Description: The critical roles of succinate and MEG3 in the metabolic changes during malignant transformation from OLP to OSCC.

References

• Ref 1: Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells .Sci Rep. 2021 Jan 19;11(1):1821. doi: 10.1038/s41598-021-81148-0. 10.1038/s41598-021-81148-0
• Ref 2: Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR 221. Mol Med Rep. 2017 Sep;16(3):2659-2667. doi: 10.3892/mmr.2017.6915. Epub 2017 Jul 4.
• Ref 3: Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of lncRNA ANRIL in tumour cells. Sci Rep. 2017 Nov 24;7(1):16231. doi: 10.1038/s41598-017-13431-y.
• Ref 4: Extreme low dose of 5-fluorouracil reverses MDR in cancer by sensitizing cancer associated fibroblasts and down-regulating P-gp. PLoS One. 2017 Jun 29;12(6):e0180023. doi: 10.1371/journal.pone.0180023. eCollection 2017.
• Ref 5: MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway. Oncol Rep. 2017 Oct;38(4):2051-2061. doi: 10.3892/or.2017.5899. Epub 2017 Aug 11.
• Ref 6: A novel miR-365-3p/EHF/keratin 16 axis promotes oral squamous cell carcinoma metastasis, cancer stemness and drug resistance via enhancing Beta5-integrin/c-met signaling pathway. J Exp Clin Cancer Res. 2019 Feb 19;38(1):89. doi: 10.1186/s13046-019-1091-5.
• Ref 7: FTY720 increases paclitaxel efficacy in cisplatin-resistant oral squamous cell carcinoma. J Oral Pathol Med. 2024 Jan;53(1):42-52.
• Ref 8: Low-Dose Perifosine, a Phase II Phospholipid Akt Inhibitor, Selectively Sensitizes Drug-Resistant ABCB1-Overexpressing Cancer Cells. Biomol Ther (Seoul). 2025 Jan 1;33(1):170-181.
• Ref 9: Hsa_circ_0005379 regulates malignant behavior of oral squamous cell carcinoma through the EGFR pathway. BMC Cancer. 2019 Apr 29;19(1):400. doi: 10.1186/s12885-019-5593-5.
• Ref 10: miR-654-5p Targets GRAP to Promote Proliferation, Metastasis, and Chemoresistance of Oral Squamous Cell Carcinoma Through Ras/MAPK Signaling. DNA Cell Biol. 2018 Apr;37(4):381-388. doi: 10.1089/dna.2017.4095. Epub 2018 Jan 24.
• Ref 11: LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression. Cancer Med. 2017 Dec;6(12):2897-2908. doi: 10.1002/cam4.1253. Epub 2017 Nov 10.
• Ref 12: The TLR3 Agonist Inhibit Drug Efflux and Sequentially Consolidates Low-Dose Cisplatin-Based Chemoimmunotherapy while Reducing Side Effects. Mol Cancer Ther. 2017 Jun;16(6):1068-1079. doi: 10.1158/1535-7163.MCT-16-0454. Epub 2017 Jan 30.
• Ref 13: MicroRNA-29a upregulates MMP2 in oral squamous cell carcinoma to promote cancer invasion and anti-apoptosis. Biomed Pharmacother. 2014 Feb;68(1):13-9. doi: 10.1016/j.biopha.2013.10.005. Epub 2013 Oct 18.
• Ref 14: PDK1 Inhibitor BX795 Improves Cisplatin and Radio-Efficacy in Oral Squamous Cell Carcinoma by Downregulating the PDK1/CD47/Akt-Mediated Glycolysis Signaling Pathway. Int J Mol Sci. 2021 Oct 25;22(21):11492.
• Ref 15: Effect of microRNA-27b on cisplatin chemotherapy sensitivity of oral squamous cell carcinoma via FZD7 signaling pathway. Oncol Lett. 2019 Jul;18(1):667-673. doi: 10.3892/ol.2019.10347. Epub 2019 May 13.
• Ref 16: RNA interference of long noncoding RNA HOTAIR suppresses autophagy and promotes apoptosis and sensitivity to cisplatin in oral squamous cell carcinoma. J Oral Pathol Med. 2018 Nov;47(10):930-937. doi: 10.1111/jop.12769. Epub 2018 Aug 27.
• Ref 17: Let-7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin-8. J Oral Pathol Med. 2018 Jul;47(6):590-597. doi: 10.1111/jop.12711. Epub 2018 Apr 17.
• Ref 18: MiR-222 targeted PUMA to improve sensitization of UM1 cells to cisplatin. Int J Mol Sci. 2014 Dec 2;15(12):22128-41. doi: 10.3390/ijms151222128.
• Ref 19: Long non-coding RNA highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma. J Cell Mol Med. 2019 Apr;23(4):2645-2655. doi: 10.1111/jcmm.14160. Epub 2019 Jan 24.
• Ref 20: TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/0008-5472.CAN-07-1420.
• Ref 21: Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance. Oral Dis. 2025 Apr;31(4):1116-1132.
• Ref 22: Metabolic reprogramming driven by METTL1-mediated tRNA m7G modification promotes acquired anlotinib resistance in oral squamous cell carcinoma. Transl Res. 2024 Jun;268:28-39.
• Ref 23: Shikonin Stimulates Mitochondria-Mediated Apoptosis by Enhancing Intracellular Reactive Oxygen Species Production and DNA Damage in Oral Cancer Cells. J Cell Biochem. 2025 Jan;126(1):e30671.
• Ref 24: Isoliquiritigenin Inhibits Oral Squamous Cell Carcinoma and Overcomes Chemoresistance by Destruction of Survivin. Am J Chin Med. 2023;51(8):2221-2241.
• Ref 25: LncRNA MEG3 contributes to adenosine-induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K-AKT-mTOR and beclin-1 signaling pathwayJ Cell Biochem. 2019 Oct;120(10):18172-18185. doi: 10.1002/jcb.29123. Epub 2019 May 29.