METTL1-m7G-EGFR/EFEMP1 axis promotes the bladder cancer development

Background The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase-like 1 (METTL1)-regulated m(7)G tRNA modification in bladder cancer (BC) remain obscure. Results In this research, we show that METTL1 was highly expressed in BC, and its level was correlated with poor patient prognosis. Silencing METTL1 suppresses the proliferation, migration and invasion of BC cells in vitro and in vivo. Multi-omics analysis reveals that METTL1-mediated m(7)G tRNA modification altered expression of certain target genes, including EGFR/EFEMP1. Mechanistically, METTL1 regulates the translation of EGFR/EFEMP1 via modifying certain tRNAs. Furthermore, forced expression of EGFR/EFEMP1 partially rescues the effect of METTL1 deletion on BC cells. Conclusions Our findings demonstrate the oncogenic role of METTL1 and the pathological significance of the METTL1-m(7)G-EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment.

Automated summary

The study reveals that METTL1 is highly expressed in bladder cancer (BC) and correlates with poor patient prognosis. Silencing METTL1 inhibits proliferation, migration, and invasion of BC cells by altering the expression of certain target genes, such as EGFR/EFEMP1, through m(7)G tRNA modification. Forced expression of EGFR/EFEMP1 partially rescues the effects of METTL1 deletion on BC cells, highlighting the potential therapeutic targets in BC treatment.