METTL3 potentiates resistance to cisplatin through m6A modification of TFAP2C in seminoma

• DOI: 10.1111/jcmm.15738
• Publication Date: 2020-08-28T22:45:00Z
• Authors: Jingchao Wei; Yinghao Yin; Jun Zhou; Hanfei Chen; Jingxuan Peng; Jianfu Yang; Yuxin Tang
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Adenosine; DNA Repair; Cell Survival; RNA Stability; Mice, Nude; RNA-Binding Proteins; Original Articles; Methyltransferases; Methylation; Seminoma; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Testicular Neoplasms; Drug Resistance, Neoplasm; Cell Line, Tumor; Animals; Humans; RNA, Messenger; Cisplatin; Protein Binding

Abstract Testicular germ cell tumours (TGCTs) rank as the most common malignancy in men aged 20‐34 years, and seminomas are type of TGCTs. As a crucial anti‐tumour agent with explicit toxicity, cisplatin may render resistance through intertwined mechanisms, even disease entities high curative ratio, such seminoma. Previously, we established cisplatin‐resistant seminoma TCam‐2 (TCam‐2/CDDP) cells showed that epigenetic regulations, non‐coding RNA (ncRNA) interactions, might orchestrate fate decisions treatment context N6‐methyladenosine (m6A) is prevalent internal modification mRNA. In present study, assessed from perspective m 6 A, another manner modification. The global A enrichment TCam‐2/CDDP was depicted. Then, elucidated whether transcription factor‐activating enhancer‐binding protein 2C (TFAP2C) functionally A‐modified by methyltransferase‐like 3 (METTL3), which acted an ‘writer’, insulin‐like growth factor 2 mRNA‐binding 1 (IGF2BP1), ‘reader’. Enhanced stability TFAP2C mRNA promoted survival under burden probably up‐regulation DNA repair‐related genes. Hopefully, this study will help improve our understanding subtleties tumour cellular coping strategy response to chemotherapy. Targeting factors involved methylation be effective for circumventing