Hepatitis B virus core protein enhances human telomerase reverse transcriptase expression and hepatocellular carcinoma cell proliferation in a c-Ets2-dependent manner

被引：23

作者：

Gai, Xiaoxiao ^{[1
,2
]}

Zhao, Peiqing ^{[1
,2
,3
]}

Pan, Yingfang ^{[1
,2
]}

Shan, Haixia ^{[1
,2
]}

Yue, Xuetian ^{[1
,2
]}

Du, Juan ^{[4
]}

Zhang, Zhenyu ^{[1
,2
]}

Liu, Peng ^{[1
,2
]}

Ma, Hongxin ^{[1
,2
]}

Guo, Min ^{[1
,2
]}

Yang, Xiaoyun ^{[5
]}

Sun, Wensheng ^{[1
,2
]}

Gao, Lifen ^{[1
,2
]}

Ma, Chunhong ^{[1
,2
]}

Liang, Xiaohong ^{[1
,2
]}

机构：

[1] Shandong Univ, Sch Med, Minist Educ, Key Lab Expt Teratol, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Sch Med, Inst Immunol, Jinan 250012, Shandong, Peoples R China

[3] Cent Hosp Zibo City, Zibo 255036, Shandong, Peoples R China

[4] Qianfo Shan Hosp, Cent Lab, Jinan 250014, Shandong, Peoples R China

[5] Shandong Univ, Qilu Hosp, Ctr Phys Examinat, Jinan 250012, Shandong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2013年 / 45卷 / 07期

基金：

美国国家科学基金会;

关键词：

Hepatitis B virus core (HBc); Hepatocellular carcinoma (HCC); Human telomerase reverse transcriptase (hTERT); Transcription activation; c-Ets2; CHRONIC LIVER-DISEASE; TRANSGENIC MICE; UP-REGULATION; MAP KINASE; GENE; PATHWAY; CANCER; ACTIVATION; HEPATOCARCINOGENESIS; PATHOGENESIS;

D O I：

10.1016/j.biocel.2013.03.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 192 and -187. 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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1174 / 1185

页数：12

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