Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
Year: 2016
Type: article
Study design: Observational Study
Abstract: // Sheng-li Yang 1, 2, * , Li-ping Liu 3, * , Leilei Niu 1 , Yun-fan Sun 4 , Xing-rong Yang 4 , Jia Fan 4 , Jian-wei Ren 1, 2 , George G. Chen 1, 2 , Paul B.S. Lai 1 1 Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China 2 Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China 3 Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, China 4 Department of Liver Surgery, Zhongshan Hospital & Liver Cancer Institute, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: George G. Chen, e-mail: [email protected] Paul B.S. Lai, e-mail: [email protected] Keywords: hepatocellular carcinoma, HIF-2α, overall survival, prognosis, apoptosis Received: September 22, 2015 Accepted: April 10, 2016 Published: April 23, 2016 ABSTRACT The role of HIF-2 α in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2 α in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2 α in 206 paired HCC and peritumoral tissues. Kaplan-Meier survival and Cox proportional hazard regression analyses were performed to identify risk factors for overall survival and recurrence-free survival in these patients. The function of HIF-2 α was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2 α in HCC tissues were lower than in peritumoral tissues, and were negatively correlated with tumor size ( P < 0.05). Kaplan-Meier survival and univariate analysis revealed that HCC patients with high HIF-2 α protein levels had longer overall survival ( P < 0.05). Over-expression of HIF-2 α induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2 α expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2 α was decreased and played an anti-tumorigenic role in HCC.
Source: Oncotarget
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2341094107