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

Abstract

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.

N7-Methylguanosine-Related lncRNAs: Integrated Analysis Associated With Prognosis and Progression in Clear Cell Renal Cell Carcinoma

“…Besides, substantial evidence also revealed the connection between the aberrant m7G RNA modification and the development of a wide range of cancers such as prostate cancer, liver cancer, lung cancer, bladder cancer, etc. ( D’Abronzo et al, 2017 ; Chen et al, 2021 ; Ma J et al, 2021 ; Ying et al, 2021 )…”

The potential role of N7-methylguanosine (m7G) in cancer

“…Intriguingly, regulators of the m7G modification are aberrantly expressed in various cancers and may act as novel biomarkers for diagnosis and prognostic prediction. The m7G regulator METTL1 is significantly overexpressed and promotes tumorigenesis and development in AML, BC, ESCC, glioma, HCC, HNSCC, ICC, LC, and NPC, and high expression levels of METTL1 often predict poor survival in these patients [ 26 , 43 , 52 , 56 , 59 , 60 , 66 , 68 , 78 ]. WDR4 is also highly expressed and increases malignant phenotypes in multiple malignancies, including AML, ESCC, HCC, HNSCC, IC, LC, and NPC.…”

“…The m7G regulators perform different roles in different types of tumors. For example, METTL1 and WDR4 play a strong carcinogenic role in AML, BC, ESCC, glioma, HCC, HNSCC, ICC, LC, and NPC, promoting the malignant phenotype and progression of tumors [ 24 , 26 , 43 , 52 , 56 , 59 , 60 , 66 , 68 , 78 ]; however, METTL1 exerts a significant anti-cancer effect in CC [ 48 ]. WBCCR22 restrains PC development, while accelerating glioma progression [ 57 , 80 ].…”

“…There has been little advancement in therapeutic strategies for BC over recent decades [ 46 ]. METTL1 is highly upregulated in BC tissues, and its expression is positively correlated with advanced clinical stage and high tumor grade [ 26 ]. METTL1 plays an oncogenic role in tumorigenesis and progression in BC.…”

CDKN3 Overcomes Bladder Cancer Cisplatin Resistance via LDHA-Dependent Glycolysis Reprogramming

“…The incidence and mortality of BLCA in men (accounting for respective 9.5 and 3.3 per 100,000 among men) are approximately 4 times those in women worldwide. 2 , 18 Despite advancements in treatment strategies, such as neoadjuvant chemotherapy, patients with advanced or metastatic BLCA frequently have a poor prognosis due to its chemoresistance. 19–21 Thus, it benefits BLCA therapy development to identify the underlying mechanisms of chemoresistance of BLCA cells.…”