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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...

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Autores principales: Yang, Sheng-li, Liu, Li-ping, Niu, Leilei, Sun, Yun-fan, Yang, Xing-rong, Fan, Jia, Ren, Jian-wei, Chen, George G., Lai, Paul B.S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085177/
https://www.ncbi.nlm.nih.gov/pubmed/27119229
http://dx.doi.org/10.18632/oncotarget.8952
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author Yang, Sheng-li
Liu, Li-ping
Niu, Leilei
Sun, Yun-fan
Yang, Xing-rong
Fan, Jia
Ren, Jian-wei
Chen, George G.
Lai, Paul B.S.
author_facet Yang, Sheng-li
Liu, Li-ping
Niu, Leilei
Sun, Yun-fan
Yang, Xing-rong
Fan, Jia
Ren, Jian-wei
Chen, George G.
Lai, Paul B.S.
author_sort Yang, Sheng-li
collection PubMed
description 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.
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spelling pubmed-50851772016-10-31 Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma Yang, Sheng-li Liu, Li-ping Niu, Leilei Sun, Yun-fan Yang, Xing-rong Fan, Jia Ren, Jian-wei Chen, George G. Lai, Paul B.S. Oncotarget Research Paper 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. Impact Journals LLC 2016-04-23 /pmc/articles/PMC5085177/ /pubmed/27119229 http://dx.doi.org/10.18632/oncotarget.8952 Text en Copyright: © 2016 Yang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yang, Sheng-li
Liu, Li-ping
Niu, Leilei
Sun, Yun-fan
Yang, Xing-rong
Fan, Jia
Ren, Jian-wei
Chen, George G.
Lai, Paul B.S.
Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
title Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
title_full Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
title_fullStr Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
title_full_unstemmed Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
title_short Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
title_sort downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085177/
https://www.ncbi.nlm.nih.gov/pubmed/27119229
http://dx.doi.org/10.18632/oncotarget.8952
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