METTL3 facilitates renal cell carcinoma progression by PLOD2 m⁶A-methylation under prolonged hypoxia.

ABSTRACT: N6-methyladenosine (m⁶A) is the most prevalent reversible modification in eukaryotic mRNA, and it plays a critical role in tumor progression. The purpose of this study was to investigate the function and regulatory mechanisms of the methyltransferase METTL3 in renal cell carcinoma (RCC). METTL3 expression was upregulated and predicted a poor prognosis in patients with advanced RCC. METTL3 facilitated the proliferation, migration, and invasion of RCC cells, depending on its methylase activity. METTL3 positively regulated the expression of PLOD2, and both genes were triggered under prolonged hypoxia. Mechanistically, hypoxia-induced the binding of HIF-1α to the METTL3 promoter, which enhanced its transcriptional activity. METTL3-mediated m⁶A modifications of PLOD2 mRNA

SUBMITTER: Chen Y 

PROVIDER: S-EPMC10794171 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature