Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis.

ABSTRACT: While the significance of acquired genetic abnormalities in the initiation of hepatocellular carcinoma (HCC) has been established, the role of epigenetic modification remains unknown. Here we identified the pivotal role of histone methyltransferase G9a in the DNA damage-triggered initiation of HCC. Using liver-specific G9a-deficient (G9a^ΔHep) mice, we revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine (DEN). In addition, pharmacological inhibition of G9a attenuated the DEN-induced initiation of HCC. After treatment with DEN, while the induction of γH2AX and p53 were comparable in the G9a^ΔHep and wild-type livers, more apoptotic hepatocytes were detected in the G9a^ΔHep liver. Transcriptome analysis identifi

SUBMITTER: Nakatsuka T 

PROVIDER: S-EPMC7815717 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature