Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1983665 | The International Journal of Biochemistry & Cell Biology | 2013 | 12 Pages |
Abstract
Hepatitis B virus core protein can regulate viral replication and host gene expression. However, it is unclear whether and how hepatitis B virus core protein regulates hepatocellular carcinoma cell proliferation. Induction of hepatitis B virus core protein over-expression significantly enhanced the proliferation of hepatocellular carcinoma cells, while knockdown of hepatitis B virus core protein expression inhibited the proliferation of hepatocellular carcinoma cells. Altered hepatitis B virus core protein expression significantly changed the growth of implanted hepatocellular carcinoma in vivo. Microarray analysis indicated that hepatitis B virus core protein up-regulated human telomerase reverse transcriptase expression, which was further validated by over-expression and knockdown assays in vitro. Furthermore, knockdown of human telomerase reverse transcriptase expression mitigated the hepatitis B virus core protein-enhanced hepatocellular carcinoma cell proliferation and clone formation in vitro. Luciferase assays indicated that hepatitis B virus core protein enhanced the promoter activity of human telomerase reverse transcriptase, which was dependent on the binding of c-Ets2 to the promoter region between â192 and â187. In addition, hepatitis B virus core protein enhanced human telomerase reverse transcriptase transcription in HepG2 cells, but not in the c-Ets2-silencing HepG2 cells. Moreover, hepatitis B virus core protein promoted c-Ets2 nuclear translocation. Finally, significantly higher levels of human telomerase reverse transcriptase expression and nuclear c-Ets2 accumulation were detected in hepatitis B virus core protein-positive hepatocellular carcinoma samples. Our findings demonstrate that hepatitis B virus core protein promotes hepatocellular carcinoma cell proliferation by up-regulating the c-Ets2-dependent expression of human telomerase reverse transcriptase.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Xiaoxiao Gai, Peiqing Zhao, Yingfang Pan, Haixia Shan, Xuetian Yue, Juan Du, Zhenyu Zhang, Peng Liu, Hongxin Ma, Min Guo, Xiaoyun Yang, Wensheng Sun, Lifen Gao, Chunhong Ma, Xiaohong Liang,