HBx genotype D represses GSTP1 expression and increases the oxidative level and apoptosis in HepG2 cells

Abstract 

Epigenetics has been implicated in human cancer development. Epigenetic factors include HBx protein, which is able to induce hypermethylation and suppresses tumor suppressor genes. One of such tumor suppressor genes, GSTP1, shows reduced expression in many human cancers. Hypermethylation of GSTP1 is the most studied mechanism of its silence. In the present study, we reported that GSTP1 expression was completely depleted in HBV integrated HepG2.2.15 cells due to the hypermethylation in its promoter region. And it was HBx, especially HBx genotype D, that played the key role in repressing GSTP1 expression. Further functional studies like ROS assay and apoptosis detection were also used to confirm this repression. Our findings should facilitate the understanding of HBV and their influences on the epigenetic modulations for epigenetic tumorigenesis during HBV-mediated hepatocellular carcinogenesis.

Keywords: HBV, HBx, DNA methylation, GSTP1, HepG2, HepG2.2.15

Abbreviations: HBV, hepatitis B virus, HBx, hepatitis B virus X, HCC, hepatocellular carcinoma, GSTP1, glutathione S-transferase P1, ROS, reactive oxygen species, DNMT1, DNA methyltransferase 1, MEM, minimal essential medium, DMEM, Dulbecco's modified Eagle's medium, PBS, phosphate-buffered saline, HBsAg, HBV surface antigen, HBcAg, HBV core antigen, MSP, methylation-specific PCR, TBHP, tert-butyl hydroperoxide