Hepatitis B virus upregulates GP73 expression by activating the HIF-2α signaling pathway

Yang,Sheng‑Li; Zeng,Cui; Fang,Xiefan; He,Qian‑Jin; Liu,Li‑Ping; Bao,Shi‑Yun; Pan,Xiaoli; Xiong,Zhi‑Fan

doi:10.3892/ol.2018.7955

Hepatitis B virus upregulates GP73 expression by activating the HIF-2α signaling pathway

Authors:
- Sheng‑Li Yang
- Cui Zeng
- Xiefan Fang
- Qian‑Jin He
- Li‑Ping Liu
- Shi‑Yun Bao
- Xiaoli Pan
- Zhi‑Fan Xiong
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Affiliations: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA, Department of General Surgery, The Center Hospital of Huanggang, Huanggang, Hubei 438000, P.R. China, Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: February 5, 2018 https://doi.org/10.3892/ol.2018.7955
Pages: 5264-5270

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Abstract

Golgi Protein 73 (GP73) is a newly identified diagnostic and prognostic marker for liver cancer. GP73 is highly expressed in liver cancer tissues, however, the mechanism of its overexpression in tumors remains unknown. In the present study, the effect of hepatitis B virus (HBV) on GP73 expression was investigated in HepG2 cells, which are negative for HBV, and in HepG2.2.12 cells, which are integrated with HBV, using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In addition, the cells were transfected with plasmid constructs overexpressing hepatitis B virus protein X (HBx), hypoxia‑inducible factor (HIF)‑1α, or HIF‑2α in order to examine their roles in GP73 expression. The results demonstrated that HBV upregulated the expression of GP73 and HIF‑2α in liver cancer cells. HIF‑2α induced the expression of GP73 in HepG2 cells and was positively correlated with GP73 expression in liver cancer tissues. By contrast, HBx and HIF‑1α did not induce GP73 expression in liver cancer cells. In summary, HBV may upregulate the expression of GP73 by activating the HIF‑2α signaling pathway. The present results may illuminate the mechanism by which GP73 is overexpressed in liver cancer tissues.

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