Disease Information

General Information of the Disease (ID: DIS00067)
Name
Tongue cancer
ICD
ICD-11: 2B62
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  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)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Cisplatin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) [1]
Resistant Disease Tongue cancer [ICD-11: 2B62.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Activation hsa05200
Ezrin/FAKT/Src signaling pathway Activation hsa05205
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC9 cells Tongue Homo sapiens (Human) CVCL_1685
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Microarray; RT-PCR
Experiment for
Drug Resistance		 MTS assay; EdU assay; Flow cytometric analysis
Mechanism Description KCNQ1OT1 promotes TSCC cell proliferation and chemo-resistance via the regulation of miR-211-5p mediated Ezrin/Fak/Src signaling.
Key Molecule: hsa-miR-483-5p [2]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Mitochondrial apoptotic signaling pathway Regulation hsa04210
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC9 cells Tongue Homo sapiens (Human) CVCL_1685
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 TUNEL assay; Flow cytometry assay
Mechanism Description FIS1 is able to regulate mitochondrial fission and cisplatin sensitivity. miR-483-5p is responsible for the downregulation of FIS1 and can suppress mitochondrial fission and apoptosis by targeting FIS1. Mitochondrial fission affects cisplatin sensitivity via the miR-483-5p-FIS1 axis in cancer cells.
Key Molecule: hsa-mir-23a [3]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
JNk signaling pathway Activation hsa04010
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
SCC4 cells Tongue Homo sapiens (Human) CVCL_1684
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-23a in both SCC-4 and Tca8113 cells markedly increased Twist expression, c-Jun N-terminal kinase (JNk) activity and the half maximal inhibitory concentration (IC50) of cisplain, and decreased cisplatin-induced apoptosis, all of which was abolished by knockdown of Twist or selective JNk inhibitor SP600125. On the other hand, knockdown of miR-23a significantly decreased Twist expression, JNk activity and IC50 of cisplain, and increased cisplatin-induced apoptosis, all of which was completely reversed by overexpression of Twist. The present study for the first time demonstrates that miR-23a promotes cisplatin chemoresistance and protects cisplatin-induced apoptosis in TSCC cells through inducing Twist expression by a JNk-dependent mechanism.
Key Molecule: hsa-mir-21 [4]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Programmed cell death 4 (PDCD4) is a tumor suppressor gene and loss of PDCD4 expression was found in multiple human cancers. PDCD4 is an important functional target of miR-21 and related to tumor invasion and transformation. miR-21 could modulate chemosensitivity of TSCC cells to cisplatin by targeting PDCD4.
Key Molecule: hsa-mir-21 [5]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-21 was found decreased as with chemosensitivity for cisplatin in the Tca/cisplatin cells.
Key Molecule: hsa-mir-214 [5]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-214 can induce cell survival and cisplatin resistance through targeting the 3'-untranslated region (UTR) of the PTEN, which leads to down-regulation of PTEN protein and activation of Akt pathway.
Key Molecule: hsa-mir-23a [5]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Topoisomerase II is involved in DNA replication, transcription and chromosome segregation, and the beta form of DNA topoisomerase II beta (TOP2B) functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. miR-23a is an up-stream regulator of TOP2B to realize the chemoresistance of cisplatin.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Glycogen synthase kinase-3 beta (GSK3B) [6]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Phosphorylation
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell metastasis Activation hsa05205
Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
Tumorigenesis Activation hsa05206
Wnt/Beta-catenin signaling pathway Activation hsa04310
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC9 cells Tongue Homo sapiens (Human) CVCL_1685
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description Overexpression of CILA1 also increased the phosphorylation of GSk-3beta, resulting resistance in tongue cancar.
Key Molecule: Long non-protein coding RNA (CILA1) [6]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
Wnt/Beta-catenin signaling pathway Activation hsa04310
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC9 cells Tongue Homo sapiens (Human) CVCL_1685
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description Overexpression of CILA1 also increased the phosphorylation of GSk-3beta, resulting resistance in tongue cancar.
Key Molecule: Polycomb complex protein BMI-1 (BMI1) [7]
Resistant Disease Tongue cancer [ICD-11: 2B62.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation SHH/GLI1 signaling pathway Activation hsa05217
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC25 cells Oral Homo sapiens (Human) CVCL_1682
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 Overexpression of BMI1 alters cell proliferation, apoptosis and stem cell self-renewal and correlates with the invasion and metastasis of several human cancers. BMI1 overexpression due to reduction of miR-200b and miR-15b may result in chemotherapy-induced EMT in TSCCs via these pathways.
Key Molecule: hsa-mir-15b [7]
Resistant Disease Tongue cancer [ICD-11: 2B62.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation SHH/GLI1 signaling pathway Activation hsa05217
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC25 cells Oral Homo sapiens (Human) CVCL_1682
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of BMI1 alters cell proliferation, apoptosis and stem cell self-renewal and correlates with the invasion and metastasis of several human cancers. BMI1 overexpression due to reduction of miR-200b and miR-15b may result in chemotherapy-induced EMT in TSCCs via these pathways.
Key Molecule: hsa-mir-200b [7]
Resistant Disease Tongue cancer [ICD-11: 2B62.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation SHH/GLI1 signaling pathway Activation hsa05217
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC25 cells Oral Homo sapiens (Human) CVCL_1682
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of BMI1 alters cell proliferation, apoptosis and stem cell self-renewal and correlates with the invasion and metastasis of several human cancers. BMI1 overexpression due to reduction of miR-200b and miR-15b may result in chemotherapy-induced EMT in TSCCs via these pathways.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Ezrin (EZR) [1]
Resistant Disease Tongue cancer [ICD-11: 2B62.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
Ezrin/FAKT/Src signaling pathway Activation hsa05205
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC9 cells Tongue Homo sapiens (Human) CVCL_1685
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay; EdU assay; Flow cytometric analysis
Mechanism Description KCNQ1OT1 promotes TSCC cell proliferation and chemo-resistance via the regulation of miR-211-5p mediated Ezrin/Fak/Src signaling.
Key Molecule: Mitochondrial fission 1 protein (FIS1) [2]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Mitochondrial apoptotic signaling pathway Regulation hsa04210
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC9 cells Tongue Homo sapiens (Human) CVCL_1685
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 TUNEL assay; Flow cytometry assay
Mechanism Description FIS1 is able to regulate mitochondrial fission and cisplatin sensitivity. miR-483-5p is responsible for the downregulation of FIS1 and can suppress mitochondrial fission and apoptosis by targeting FIS1. Mitochondrial fission affects cisplatin sensitivity via the miR-483-5p-FIS1 axis in cancer cells.
Key Molecule: Twist-related protein 1 (TWST1) [3]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
JNk signaling pathway Activation hsa04010
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
SCC4 cells Tongue Homo sapiens (Human) CVCL_1684
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-23a in both SCC-4 and Tca8113 cells markedly increased Twist expression, c-Jun N-terminal kinase (JNk) activity and the half maximal inhibitory concentration (IC50) of cisplain, and decreased cisplatin-induced apoptosis, all of which was abolished by knockdown of Twist or selective JNk inhibitor SP600125. On the other hand, knockdown of miR-23a significantly decreased Twist expression, JNk activity and IC50 of cisplain, and increased cisplatin-induced apoptosis, all of which was completely reversed by overexpression of Twist. The present study for the first time demonstrates that miR-23a promotes cisplatin chemoresistance and protects cisplatin-induced apoptosis in TSCC cells through inducing Twist expression by a JNk-dependent mechanism.
Key Molecule: Programmed cell death protein 4 (PDCD4) [4]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Programmed cell death 4 (PDCD4) is a tumor suppressor gene and loss of PDCD4 expression was found in multiple human cancers. PDCD4 is an important functional target of miR-21 and related to tumor invasion and transformation. miR-21 could modulate chemosensitivity of TSCC cells to cisplatin by targeting PDCD4.
Key Molecule: DNA topoisomerase 2-beta (TOP2B) [5]
Resistant Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Topoisomerase II is involved in DNA replication, transcription and chromosome segregation, and the beta form of DNA topoisomerase II beta (TOP2B) functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. miR-23a is an up-stream regulator of TOP2B to realize the chemoresistance of cisplatin.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-203 [8]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
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
PIk3CA signaling pathway Regulation hsa04211
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-203 expression is much lower in the clinical tongue cancer samples. In the surviving Tca8113 cells after cisplatin treatment, miR-203 expression was much lower. Delivery of miR-203 sensitized the Tca8113 cells to cisplatin induced cell death through downregulation of PIk3CA.
Key Molecule: hsa-mir-21 [9]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model CA-27 cells Mouth Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Down-regulation of miR-21 could sensitize CA-27 cells to cisplatin possibly by increasing cisplatin induced apoptosis.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: hsa-miR-485-5p [10]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model SCC25 cells Oral Homo sapiens (Human) CVCL_1682
SCC25-res cells Tongue Homo sapiens (Human) CVCL_A5BQ
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; BrdU incorporation assay
Mechanism Description Hsa-miR485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAk1 in oral tongue squamous cell carcinom. Overexpression of p21 (RAC1) activated kinase 1 (PAk1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells.
Key Molecule: Serine/threonine-protein kinase PAK 1 (PAK1) [10]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Epithelial mesenchymal transition signaling pathway Inhibition hsa01521
In Vitro Model SCC25 cells Oral Homo sapiens (Human) CVCL_1682
SCC25-res cells Tongue Homo sapiens (Human) CVCL_A5BQ
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; BrdU incorporation assay
Mechanism Description Hsa-miR485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAk1 in oral tongue squamous cell carcinom. Overexpression of p21 (RAC1) activated kinase 1 (PAk1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells.
Key Molecule: hsa-mir-15b [11]
Sensitive Disease Oral tongue squamous cell cancer [ICD-11: 2B62.3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SCC25 cells Oral Homo sapiens (Human) CVCL_1682
SCC25-res cells Tongue Homo sapiens (Human) CVCL_A5BQ
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay; Soft agar assay
Mechanism Description miR15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer Overexpression of TRIM14 induced EMT phenotype.
Key Molecule: Tripartite motif-containing protein 14 (TRIM14) [11]
Sensitive Disease Oral tongue squamous cell cancer [ICD-11: 2B62.3]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SCC25 cells Oral Homo sapiens (Human) CVCL_1682
SCC25-res cells Tongue Homo sapiens (Human) CVCL_A5BQ
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Soft agar assay
Mechanism Description miR15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer Overexpression of TRIM14 induced EMT phenotype.
Key Molecule: hsa-mir-181a [12]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
miR181a-Twist1 signaling pathway Regulation hsa05206
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC15 cells Tongue Homo sapiens (Human) CVCL_1681
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Cisplatin chemoresistance induced EMT, enhanced metastatic potential and down-regulated miR-181a in TSCC cells, miR-181a directly targeted Twist1 and then reversed chemoresistance and EMT in TSCC cells, miR-181a-Twist1 pathway may play an important role in the development of cisplatin-chemoresistance.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA) [8]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
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
PIk3CA signaling pathway Regulation hsa04211
In Vitro Model Tca8113 cells Tongue Homo sapiens (Human) CVCL_6851
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-203 expression is much lower in the clinical tongue cancer samples. In the surviving Tca8113 cells after cisplatin treatment, miR-203 expression was much lower. Delivery of miR-203 sensitized the Tca8113 cells to cisplatin induced cell death through downregulation of PIk3CA.
Key Molecule: Twist-related protein 1 (TWST1) [12]
Sensitive Disease Tongue squamous cell carcinoma [ICD-11: 2B62.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
miR181a-Twist1 signaling pathway Regulation hsa05206
In Vitro Model CAL27 cells Oral Homo sapiens (Human) CVCL_1107
SCC15 cells Tongue Homo sapiens (Human) CVCL_1681
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Cisplatin chemoresistance induced EMT, enhanced metastatic potential and down-regulated miR-181a in TSCC cells, miR-181a directly targeted Twist1 and then reversed chemoresistance and EMT in TSCC cells, miR-181a-Twist1 pathway may play an important role in the development of cisplatin-chemoresistance.
References
Ref 1 LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling. Cell Death Dis. 2018 Jul 3;9(7):742. doi: 10.1038/s41419-018-0793-5.
Ref 2 miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1. Cancer Lett. 2015 Jul 1;362(2):183-91. doi: 10.1016/j.canlet.2015.03.045. Epub 2015 Apr 2.
Ref 3 miR-23a promotes cisplatin chemoresistance and protects against cisplatin-induced apoptosis in tongue squamous cell carcinoma cells through Twist. Oncol Rep. 2015 Feb;33(2):942-50. doi: 10.3892/or.2014.3664. Epub 2014 Dec 10.
Ref 4 MiR-21 modulates chemosensitivity of tongue squamous cell carcinoma cells to cisplatin by targeting PDCD4. Mol Cell Biochem. 2014 May;390(1-2):253-62. doi: 10.1007/s11010-014-1976-8. Epub 2014 Mar 11.
Ref 5 MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines. Oral Oncol. 2010 Apr;46(4):317-22. doi: 10.1016/j.oraloncology.2010.02.002. Epub 2010 Mar 9.
Ref 6 Chemotherapy-Induced Long Non-coding RNA 1 Promotes Metastasis and Chemo-Resistance of TSCC via the Wnt/Beta-Catenin Signaling Pathway. Mol Ther. 2018 Jun 6;26(6):1494-1508. doi: 10.1016/j.ymthe.2018.04.002. Epub 2018 Apr 5.
Ref 7 MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting BMI1. Oncogene. 2012 Jan 26;31(4):432-45. doi: 10.1038/onc.2011.263. Epub 2011 Jul 4.
Ref 8 miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer. Biochem Biophys Res Commun. 2016 Apr 29;473(2):382-7. doi: 10.1016/j.bbrc.2016.02.105. Epub 2016 Mar 3.
Ref 9 miR-21 inhibitor sensitizes human OSCC cells to cisplatin. Mol Biol Rep. 2012 May;39(5):5481-5. doi: 10.1007/s11033-011-1350-9. Epub 2012 Jan 15.
Ref 10 hsa-miR-485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma. Int J Mol Med. 2017 Jul;40(1):83-89. doi: 10.3892/ijmm.2017.2992. Epub 2017 May 16.
Ref 11 miR-15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer. Oncol Rep. 2017 May;37(5):2720-2726. doi: 10.3892/or.2017.5532. Epub 2017 Mar 27.
Ref 12 miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma. Biochem Biophys Res Commun. 2013 Nov 15;441(2):364-70. doi: 10.1016/j.bbrc.2013.10.051. Epub 2013 Oct 19.

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