METTL1 drives tumor progression of bladder cancer via degrading ATF3 mRNA in an m7G-modified miR-760-dependent manner

METTL1 以 m7G 修饰的 miR-760 依赖的方式降解 ATF3 mRNA 来驱动膀胱癌肿瘤进展

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作者:Haiyun Xie #, Mingchao Wang #, Haifeng Yu #, Huan Wang, Lifeng Ding, Ruyue Wang, Wenqin Luo, Zeyi Lu, Qiming Zheng, Liangliang Ren, Zhenwei Zhou, Wenjing Su, Liqun Xia, Gonghui Li

Abstract

7-methylguanosine (m7G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m7G modification, METTL1 has been reported in certain human cancers. However, the role of internal m7G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m7G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m7G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m7G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.

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