Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
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AbstractThe role of HIF-2a in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2a in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2a 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-2a was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2a 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-2a protein levels had longer overall survival (P < 0.05). Over-expression of HIF-2a induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2a expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2a was decreased and played an anti-tumorigenic role in HCC.
All Author(s) ListYang SL, Liu LP, Niu L, Sun YF, Yang XR, Fan J, Ren JW, Chen GG, Lai PBS
Journal nameOncotarget
Volume Number7
Issue Number23
Pages34571 - 34581
LanguagesEnglish-United Kingdom
Keywordsapoptosis; hepatocellular carcinoma; HIF-2 alpha; overall survival; prognosis
Web of Science Subject CategoriesCell Biology; Oncology

Last updated on 2020-26-10 at 00:30