Open AccessMETTL3/YTHDF2 m 6 A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer
Author(s) -
Xie Haiyun,
Li Jiangfeng,
Ying Yufan,
Yan Huaqing,
Jin Ke,
Ma Xueyou,
He Liujia,
Xu Xin,
Liu Ben,
Wang Xiao,
Zheng Xiangyi,
Xie Liping
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15063
Subject(s) - klf4 , carcinogenesis , cancer research , messenger rna , bladder cancer , biology , cancer , transcriptome , small hairpin rna , rna , microbiology and biotechnology , gene expression , gene , transcription factor , genetics , sox2
Abstract N6‐Methyladenosine (m 6 A) modification, the most prevalent modification of eukaryotic messenger RNA (mRNA), is involved in the progression of various tumours. However, the specific role of m 6 A in bladder cancer (BCa) is still poorly understood. In this study, we demonstrated the tumour‐promoting function and specific regulatory mechanism of m 6 A axis, consisting of the core ‘writer’ protein METTL3 and the major reader protein YTHDF2. Depletion of METTL3 impaired cancer proliferation and cancer metastasis in vitro and in vivo. Through transcriptome sequencing, m 6 A methylated RNA immunoprecipitation (MeRIP) and RIP, we determined that the METTL3/YTHDF2 m 6 A axis directly degraded the mRNAs of the tumour suppressors SETD7 and KLF4, contributing to the progression of BCa. In addition, overexpression of SETD7 and KLF4 revealed a phenotype consistent with that induced by depletion of the m 6 A axis. Thus, our findings on the METTL3/YTHDF2/SETD7/KLF4 m 6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for BCa.