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

共 49 条

[31] Hepatitis B Virus X Protein Upregulates hELG1/ATAD5 Expression through E2F1 in Hepatocellular Carcinoma [J].

Ghosh, Alip ;

Ghosh, Suchandrima ;

Dasgupta, Debanjali ;

Ghosh, Amit ;

Datta, Somenath ;

Sikdar, Nilabja ;

Datta, Simanti ;

Chowdhury, Abhijit ;

Banerjee, Soma .

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2016, 12 (01) :30-41

[32] The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress [J].

Moghadam, Delaram ;

Zarei, Reza ;

Vakili, Sina ;

Ghojoghi, Rozita ;

Zarezade, Vahid ;

Veisi, Ali ;

Sabaghan, Mohamad ;

Azadbakht, Omid ;

Behrouj, Hamid .

MOLECULAR BIOLOGY REPORTS, 2023, 50 (01) :77-84

[33] Hepatitis C virus core protein enhances HIV-1 replication in human macrophages through TLR2, JNK, and MEK1/2-dependent of TNF-α and IL-6 [J].

Swaminathan, Gokul ;

Pascual, Daniel ;

Rival, Germaine ;

Perales-Linares, Renzo ;

Martin-Garcia, Julio ;

Navas-Martin, Sonia .

FEBS LETTERS, 2014, 588 (18) :3501-3510

[34] RNA methyltransferase NSUN2 promotes hypopharyngeal squamous cell carcinoma proliferation and migration by enhancing TEAD1 expression in an m5C-dependent manner [J].

Chen, Lixiao ;

Ding, Jian ;

Wang, Baoxin ;

Chen, Xinwei ;

Ying, Xinjiang ;

Yu, Ziwei ;

Dong, Pin .

EXPERIMENTAL CELL RESEARCH, 2021, 404 (02)

[35] Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2 [J].

Li, Weihua ;

Miao, Xiaohui ;

Qi, Zhongtian ;

Zeng, Wenting ;

Liang, Jianxin ;

Liang, Zengwei .

VIROLOGY JOURNAL, 2010, 7

[36] Hepatitis B doubly spliced protein (HBDSP) promotes hepatocellular carcinoma cell apoptosis via ETS1/GATA2/YY1-mediated p53 transcription [J].

Xu, Xiazhen ;

Zhang, Lu ;

Ye, Guiying ;

Shi, Jiajian ;

Peng, Yibin ;

Xin, Fan ;

Lin, Yi ;

Wu, Qiong ;

Lin, Xu ;

Chen, Wannan .

JOURNAL OF VIROLOGY, 2023, 97 (11)

[37] The imbalance between NKG2A and NKG2D expression is involved in NK cell immunosuppression and tumor progression of patients with hepatitis B virus-related hepatocellular carcinoma [J].

Yu, Lihua ;

Sun, Lei ;

Liu, Xiaoli ;

Wang, Xinhui ;

Yan, Huiwen ;

Pu, Qing ;

Xie, Yuqing ;

Jiang, Yuyong ;

Du, Juan ;

Yang, Zhiyun .

HEPATOLOGY RESEARCH, 2023, 53 (05) :417-431

[38] Epidermal growth factor receptor inhibitor AG1478 affects HepG2 cell proliferation, cell cycle, apoptosis and c-Myc protein expression in a dose-dependent manner [J].

Wang, Wenqi ;

Yan, Mingxian ;

Liu, Changhong ;

Wang, Yiguo ;

Wang, Yaru ;

Wang, Liyun ;

Fan, Jinhua .

BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT, 2018, 32 (04) :1021-1027

[39] F-Box Protein 43, Stabilized by N6-Methyladenosine Methylation, Enhances Hepatocellular Carcinoma Cell Growth and Invasion via Promoting p53 Degradation in a Ubiquitin Conjugating Enzyme E2 C-Dependent Manner [J].

Zhou, Huijun ;

Zeng, Chong ;

Liu, Jie ;

Luo, Haijun ;

Huang, Wei .

CANCERS, 2023, 15 (03)

[40] Bardoxolone Methyl Suppresses Hepatitis B Virus Large Surface Protein Variant W4P-Related Carcinogenesis and Hepatocellular Carcinoma Cell Proliferation Via the Inhibition of Signal Transducer and Activator of Transcription 3 Signaling [J].

Gee, Min Sung ;

Kang, Sung-Bae ;

Kim, Namkwon ;

Choi, Jiyoon ;

Kim, Nam-Jung ;

Kim, Bum-Joon ;

Inn, Kyung-Soo ;

Lee, Jong Kil .

PHARMACOLOGY, 2018, 102 (1-2) :105-113

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