Hepatitis B Virus Infection Dampens CtIP Expression in Hepatoma Cell.

Abstract

Hepatitis B virus (HBV) infection is a leading cause for hepatocellular carcinoma (HCC). Dysregulation of DNA double-strand break (DSB) repair may explain the pathogenesis of HBV-related HCC. Tumor suppressor CtIP plays a critical role in DSB repair. The purpose of present study was to clarify whether HBV affects CtIP expression in DSB repair of hepatoma cell. HepG2.2.15 was selected as the HBV positive hepatoma cell line, while HepG2 as the HBV negative hepatoma cell line. The two cell lines were treated with bleomycin to induce DSB. Bleomycin treatment could result in DSB by γ-H2AX detection. CtIP gene expression was significantly upregulated after DSB in both HepG2 and HepG2.2.15, while CtIP expression of HepG2.2.15 was higher than that observed in HepG2 before and after DSB. CtIP protein expression was the same pattern as its gene expression. Phosphorylated CtIP (p-CtIP, serine site) was even lower than detectable limit in both HepG2 and HepG2.2.15 before DSB. However, p-CtIP of HepG2.2.15 was significantly lower than that of HepG2 after DSB. These results suggest that HBV could interfere CtIP via enhancing its expression while dampening its phosphorylation, which may disrupt DSB repair pathways and implicate CtIP dysfunction in HBV-related HCC.