O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N⁶-methyladenosine-dependent manner.

ABSTRACT: Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), but its pathogenic mechanism remains to be explored. The RNA N⁶-methyladenosine (m⁶A) reader, YTH (YT521-B homology) domain 2 (YTHDF2), plays a critical role in the HCC progression. However, the function and regulatory mechanisms of YTHDF2 in HBV-related HCC remain largely elusive. Here, we discovered that YTHDF2 O-GlcNAcylation was markedly increased upon HBV infection. O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation of YTHDF2 on serine 263 enhanced its protein stability and oncogenic activity by inhibiting its ubiquitination. Mechanistically, YTHDF2 stabilized minichromosome maintenance protein 2 (MCM2) and MCM5 transcripts in an m⁶A-dependent manner, thus pro

SUBMITTER: Yang Y 

PROVIDER: S-EPMC9918532 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature