Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma.

ABSTRACT: The role of HIF-2? in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2? in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2? 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? was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2? 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? protein levels had longer overall survival (P < 0.05). Over-expression of HIF-2? induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2? expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2? was decreased and played an anti-tumorigenic role in HCC.

SUBMITTER: Yang SL 

PROVIDER: S-EPMC5085177 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other