Name	Testicular cancer
ICD	ICD-11: 2C80

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	3-Methyladenine		Investigative	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	VIRMA has an oncogenic role in germ cell tumor confirming our previous tissue-based study and is further involved in response to cisplatin by interfering with DNA repair. Enhanced response to cisplatin after VIRMA knockdown was related to significant increase in DNA damage (with higher Gamma-H2AX and GADD45B levels) and downregulation of XLF and Double-strand break repair protein MRE11 (MRE11).
Responsed Disease	Germ cell tumour of testis [ICD-11: 2C80.2]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	2102EP	Embryonal carcinoma	Homo sapiens	CVCL_C522
	NCC-IT	Testicular embryonal carcinoma	Homo sapiens	CVCL_1451
	NT2	Malignant neoplasms	Mus musculus	CVCL_JA57
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	VIRMA has an oncogenic role in germ cell tumor confirming our previous tissue-based study and is further involved in response to cisplatin by interfering with DNA repair. Enhanced response to cisplatin after VIRMA knockdown was related to significant increase in DNA damage (with higher Histone H2AX (H2AX) and GADD45B levels) and downregulation of XLF and MRE11.
Responsed Disease	Germ cell tumour of testis [ICD-11: 2C80.2]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	2102EP	Embryonal carcinoma	Homo sapiens	CVCL_C522
	NCC-IT	Testicular embryonal carcinoma	Homo sapiens	CVCL_1451
	NT2	Malignant neoplasms	Mus musculus	CVCL_JA57
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	VIRMA has an oncogenic role in germ cell tumor confirming our previous tissue-based study and is further involved in response to cisplatin by interfering with DNA repair. Enhanced response to cisplatin after VIRMA knockdown was related to significant increase in DNA damage (with higher Gamma-H2AX and Negative growth regulatory protein MyD118 (GADD45B) levels) and downregulation of XLF and MRE11.
Responsed Disease	Germ cell tumour of testis [ICD-11: 2C80.2]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	2102EP	Embryonal carcinoma	Homo sapiens	CVCL_C522
	NCC-IT	Testicular embryonal carcinoma	Homo sapiens	CVCL_1451
	NT2	Malignant neoplasms	Mus musculus	CVCL_JA57
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	VIRMA has an oncogenic role in germ cell tumor confirming our previous tissue-based study and is further involved in response to cisplatin by interfering with DNA repair. Enhanced response to cisplatin after VIRMA knockdown was related to significant increase in DNA damage (with higher Gamma-H2AX and GADD45B levels) and downregulation of Non-homologous end-joining factor 1 (NHEJ1/XLF) and MRE11.
Responsed Disease	Germ cell tumour of testis [ICD-11: 2C80.2]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	2102EP	Embryonal carcinoma	Homo sapiens	CVCL_C522
	NCC-IT	Testicular embryonal carcinoma	Homo sapiens	CVCL_1451
	NT2	Malignant neoplasms	Mus musculus	CVCL_JA57
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	METTL3 potentiates resistance to cisplatin through m6A modification of Transcription factor AP-2 gamma (TFAP2C) in seminoma. Enhanced stability of TFAP2C mRNA promoted seminoma cell survival under cisplatin treatment burden probably through up-regulation of DNA repair-related genes. IGF2BP1 binds to TFAP2C and enhances TFAP2C mRNA stability.
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
In-vivo Model	Male mice were subcutaneously injected with tumour cells near the limbs to establish xenografts (1 × 106/mouse, 0.2 mL for each injection site; METTL3-overexpressing TCam-2/CDDP cells were inoculated once at the initial time and IGF2BP1-inhibited TCam-2/CDDP cells were inoculated every 3 days).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	METTL3 potentiates resistance to cisplatin through m6A modification of Transcription factor AP-2 gamma (TFAP2C) in seminoma. Enhanced stability of TFAP2C mRNA promoted seminoma cell survival under cisplatin treatment burden probably through up-regulation of DNA repair-related genes. IGF2BP1 binds to TFAP2C and enhances TFAP2C mRNA stability.
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
In-vivo Model	Male mice were subcutaneously injected with tumour cells near the limbs to establish xenografts (1 × 106/mouse, 0.2 mL for each injection site; METTL3-overexpressing TCam-2/CDDP cells were inoculated once at the initial time and IGF2BP1-inhibited TCam-2/CDDP cells were inoculated every 3 days).

Ref 1	The m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting ATG5 in seminoma. Transl Androl Urol. 2021 Apr;10(4):1711-1722. doi: 10.21037/tau-20-1411.
Ref 2	The component of the m(6)A writer complex VIRMA is implicated in aggressive tumor phenotype, DNA damage response and cisplatin resistance in germ cell tumors. J Exp Clin Cancer Res. 2021 Aug 25;40(1):268. doi: 10.1186/s13046-021-02072-9.
Ref 3	METTL3 potentiates resistance to cisplatin through m(6) A modification of TFAP2C in seminoma. J Cell Mol Med. 2020 Oct;24(19):11366-11380. doi: 10.1111/jcmm.15738. Epub 2020 Aug 28.