METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N⁶-methyladenosine-dependent YTHDF binding.

ABSTRACT: The adenomatous polyposis coli (APC) is a frequently mutated tumour suppressor gene in cancers. However, whether APC is regulated at the epitranscriptomic level remains elusive. In this study, we analysed TCGA data and separated 200 paired oesophageal squamous cell carcinoma (ESCC) specimens and their adjacent normal tissues and demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in tumour tissues. m⁶A-RNA immunoprecipitation sequencing revealed that METTL3 upregulates the m⁶A modification of APC, which recruits YTHDF for APC mRNA degradation. Reduced APC expression increases the expression of β-catenin and β-catenin-mediated cyclin D1, c-Myc, and PKM2 expression, thereby leading to enhanced aerobic glycolysis, ESCC cell proliferation, and tumour f

SUBMITTER: Wang W 

PROVIDER: S-EPMC8217513 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature