Abstract
Chronic infection with the hepatitis B virus (HBV) remains one of the primary drivers of the development of hepatocellular carcinoma (HCC), a highly aggressive malignancy with a grim prognosis. This study focused on the role of E1A-binding protein p300 (EP300) in the malignant phenotype of HBV-positive HCC cells and its functional mechanism. Increased EP300 expression was detected in HBV-positive tumor tissues and cells compared to their control counterparts. Silencing EP300 reduced tumorigenic activity, proliferation, viability, migration, invasion, and resistance to apoptosis of HBV-positive cells and reduced the concentrations of HBV infection markers HBsAg and HBeAg. These effects were achieved, at least in part, through downregulation of minichromosome maintenance 8 homologous recombination repair factor (MCM8). MCM8 was identified as a target of EP300 and mediated by acetylation modification. MCM8 was upregulated in HBV-positive tumors and HCC cells while decreasing following EP300 silencing in cells. However, the restoration of MCM8 expression in these cells rescued their malignant properties. In summary, this study suggests a role for EP300-mediated MCM8 upregulation in the malignant properties of HBV-positive HCC.