Deficiency of TET2-mediated KMT2D self-transcription confers a targetable vulnerability in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) has become a leading cause of cancer-related mortality worldwide. Conventional therapies tend to exacerbate comorbidities, liver dysfunction, and relapse, rendering an urgent demand for novel strategy for management of HCC. Here, we reported that DNA dioxygenase TET2 collaborates with histone methyltransferase KMT2D to enable transcription of KMT2D and ARID1A in HCC. Mechanistically, KMT2D and ARID1A are the major epigenetic targets of TET2 through RNA-seq analysis. Moreover, KMT2D recruits TET2 to facilitate self-transcription via oxidation of 5-methylcytosine in promoter, thereby maintaining expression of ARID1A. Physiologically, KMT2D was identified as a tumor suppressor and mediates the antitumor effect of vitamin C in HCC. Tum

SUBMITTER: Jin Y 

PROVIDER: S-EPMC11574621 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature