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

7-methylguanosine (m(7)G) 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 m(7)G modification, METTL1 has been reported in certain human cancers. However, the role of internal m(7)G 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, m(7)G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m(7)G-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/m(7)G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.

Automated summary

The m(7)G modification is found to be present in RNA internal positions and plays a crucial role in the proliferation and metastasis of bladder cancer. METTL1 is shown to promote the processing of miR-760 in an m(7)G-dependent manner and indirectly degrade tumor suppressor ATF3 mRNA.