Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma.
The role of HIF-2α in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2α in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2α 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-2α was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2α 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-2α protein levels had longer overall survival (P < 0.05). Over-expression of HIF-2α induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2α expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2α was decreased and played an anti-tumorigenic role in HCC.
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
Sheng-Li
SL
Yang
Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
Li-Ping
LP
Liu
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Leilei
L
Niu
Department of Liver Surgery, Zhongshan Hospital & Liver Cancer Institute, Fudan University, Shanghai, China.
Yun-Fan
YF
Sun
Department of Liver Surgery, Zhongshan Hospital & Liver Cancer Institute, Fudan University, Shanghai, China.
Xing-Rong
XR
Yang
Department of Liver Surgery, Zhongshan Hospital & Liver Cancer Institute, Fudan University, Shanghai, China.
Jia
J
Fan
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
Jian-Wei
JW
Ren
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
George G
GG
Chen
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Paul B S
PB
Lai
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D015536:Down-Regulation; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014183:Transplantation, Heterologous; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C494772:BAK1 protein, human; C114487:PDCD4 protein, human; C110951:ZNF148 protein, human
HIF-2α; apoptosis; hepatocellular carcinoma; overall survival; prognosis