HBx genotype D represses GSTP1 expression and increases the oxidative level and apoptosis in HepG2 cells.
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.
Niu
Dandan
D
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
Zhang
Jianhua
J
Ren
Yudan
Y
Feng
Huixing
H
Chen
Wei Ning
WN
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000032:analysis; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D017382:Reactive Oxygen Species; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051549:Glutathione S-Transferase pi