METTL1-m G-EGFR/EFEMP1 轴促进膀胱癌的发展。

METTL1-m G-EGFR/EFEMP1 axis promotes the bladder cancer development.

机构信息

Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

出版信息

Clin Transl Med. 2021 Dec;11(12):e675. doi: 10.1002/ctm2.675.

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 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 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 G-EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment.

背景

转移 RNA（tRNA）的转录后修饰对于 tRNA 的功能的各个方面都是至关重要的，并且已经涉及到许多人类癌症的肿瘤发生和进展。相比之下，甲基转移酶样 1（METTL1）调节的 m G tRNA 修饰在膀胱癌（BC）中的生物学功能仍不清楚。

结果

在这项研究中，我们表明 METTL1 在 BC 中高度表达，其水平与患者预后不良相关。沉默 METTL1 抑制 BC 细胞的体外和体内增殖、迁移和侵袭。多组学分析显示，METTL1 介导的 m G tRNA 修饰改变了某些靶基因的表达，包括 EGFR/EFEMP1。机制上，METTL1 通过修饰某些 tRNA 来调节 EGFR/EFEMP1 的翻译。此外，EGFR/EFEMP1 的强制表达部分挽救了 METTL1 缺失对 BC 细胞的影响。