Disease Information

General Information of the Disease (ID: DIS00095)
Name
Testicular cancer
ICD
ICD-11: 2C80
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  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
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: H19, imprinted maternally expressed transcript (H19) [1]
Resistant Disease Seminoma [ICD-11: 2C80.3]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Testicular cancer [ICD-11: 2C80]
The Specified Disease Testicular germ cell tumor
The Studied Tissue Testis
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.09E-08
Fold-change: 3.91E+00
Z-score: 6.05E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT/mTOR signaling pathway Regulation N.A.
In Vitro Model TCam-2 cells Testicle Homo sapiens (Human) CVCL_T012
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.
Key Molecule: hsa-miR-106b-5p [1]
Resistant Disease Seminoma [ICD-11: 2C80.3]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT/mTOR signaling pathway Regulation N.A.
In Vitro Model TCam-2 cells Testicle Homo sapiens (Human) CVCL_T012
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.
Key Molecule: hsa-miR-106b-5p [1]
Resistant Disease Seminoma [ICD-11: 2C80.3]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT/mTOR signaling pathway Regulation N.A.
In Vitro Model TCam-2 cells Testicle Homo sapiens (Human) CVCL_T012
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.
Key Molecule: hsa-miR-371a [2]
Resistant Disease Testicular germ cell tumor [ICD-11: 2C80.0]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NCCIT cells Embryo Homo sapiens (Human) CVCL_1451
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 Crystal violet assay; Flow cytometry assay
Mechanism Description MicroRNA-371a-3p (miR-371), the new serum biomarker for TGCTs, shows significantly increased expression in cisplatin-resistant TGCT cell lines compared to sensitive parental cell lines. However, the functional impact of miR-371 on cisplatin sensitivity has not been investigated yet. To evaluate the impact of miR-371 on cisplatin sensitivity, antagomirs were used to inhibit miR-371 expression, resulting in a > 98% decrease in miR-371 expression. Cisplatin sensitivity was significantly increased after miR-371 inhibition in cisplatin-resistant and corresponding parental TGCT cell lines, indicating a strongly reduced viability and increased apoptosis after cisplatin treatment in miR-371-inhibited cells. Our results suggest that miR-371 may contribute to the development of cisplatin resistance in TGCTs. Interfering with miR-371 expression can increase the cisplatin sensitivity of tumour cells, which may represent a promising approach to improve future therapeutic outcomes in patients with TGCTs, especially those with cisplatin-resistant disease.
Key Molecule: hsa-miR-371a-3p [2]
Resistant Disease Testicular germ cell tumor [ICD-11: 2C80.0]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NCCIT cells Embryo Homo sapiens (Human) CVCL_1451
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 Crystal violet assay; Flow cytometry assay
Mechanism Description MicroRNA-371a-3p (miR-371), the new serum biomarker for TGCTs, shows significantly increased expression in cisplatin-resistant TGCT cell lines compared to sensitive parental cell lines. However, the functional impact of miR-371 on cisplatin sensitivity has not been investigated yet. To evaluate the impact of miR-371 on cisplatin sensitivity, antagomirs were used to inhibit miR-371 expression, resulting in a > 98% decrease in miR-371 expression. Cisplatin sensitivity was significantly increased after miR-371 inhibition in cisplatin-resistant and corresponding parental TGCT cell lines, indicating a strongly reduced viability and increased apoptosis after cisplatin treatment in miR-371-inhibited cells. Our results suggest that miR-371 may contribute to the development of cisplatin resistance in TGCTs. Interfering with miR-371 expression can increase the cisplatin sensitivity of tumour cells, which may represent a promising approach to improve future therapeutic outcomes in patients with TGCTs, especially those with cisplatin-resistant disease.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Testis development-related protein 1 (TDRG1) [1]
Resistant Disease Seminoma [ICD-11: 2C80.3]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT/mTOR signaling pathway Regulation N.A.
In Vitro Model TCam-2 cells Testicle Homo sapiens (Human) CVCL_T012
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.
Key Molecule: G1/S-specific cyclin-D1 (CCND1) [3]
Resistant Disease Testicular germ cell tumor [ICD-11: 2C80.2]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Susa cells Thyroid gland Homo sapiens (Human) CVCL_L280
GCT27 cells Thyroid gland Homo sapiens (Human) CVCL_A344
833K cells Abdomen Homo sapiens (Human) CVCL_2292
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 ATP cell viability assay
Mechanism Description CCND1 may induce cisplatin resistance both through cell cycle control and inhibition of cellular apoptosis pathways, which have been previously observed37 and supported by our CCND1 knockdown study. The role of CCND1 in cell cycle control is well documented. CCND1 accumulates in cells at middle and late G1 phase and stimulate G1 progression to S phase. The proportion of parental cells in G1/0 correlated with the cisplatin sensitivity, with 833K cells having the highest G1/0 population cells and lowest EC50 value and GCT27 the lowest G1/0 population but highest EC50 score.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-302a [4]
Sensitive Disease Testicular embryonal carcinoma [ICD-11: 2C80.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model NCCIT cells Embryo Homo sapiens (Human) CVCL_1451
NT2 cells Prostate Homo sapiens (Human) CVCL_JA57
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Up-regulation of miR-302a significantly increased the sensitivity of NT2 cells to cisplatin by enhancing cisplatin-induced G2/M phase arrest and the subsequent progression to apoptosis.
References
Ref 1 Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma. Cancer Med. 2018 Dec;7(12):6247-6257. doi: 10.1002/cam4.1871. Epub 2018 Nov 14.
Ref 2 MicroRNA-212-3p inhibits paclitaxel resistance through regulating epithelial-mesenchymal transition, migration and invasion by targeting ZEB2 in human hepatocellular carcinoma. Oncol Lett. 2020 Oct 20(4):23
Ref 3 The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers .Am J Pathol. 2010 Jun;176(6):2607-15. doi: 10.2353/ajpath.2010.090780. Epub 2010 Apr 15. 10.2353/ajpath.2010.090780
Ref 4 MicroRNA-302a sensitizes testicular embryonal carcinoma cells to cisplatin-induced cell death. J Cell Physiol. 2013 Dec;228(12):2294-304. doi: 10.1002/jcp.24394.

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