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γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition

Hepatocellular carcinoma (HCC) is one of the most deadly cancers. Using mRNA microarray analysis, we found that H2AX decreased under hypoxic conditions. Hypoxia is an important physiological and pathological stress that induces H2AX phosphorylation (γ-H2AX), but the regulatory mechanism of γ-H2AX re...

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Autores principales: Xiao, Heng, Tong, Rongliang, Ding, Chaofeng, Lv, Zhen, Du, Chengli, Peng, Chuanhui, Cheng, Shaobing, Xie, Haiyang, Zhou, Lin, Wu, Jian, Zheng, Shusen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385844/
https://www.ncbi.nlm.nih.gov/pubmed/25537504
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author Xiao, Heng
Tong, Rongliang
Ding, Chaofeng
Lv, Zhen
Du, Chengli
Peng, Chuanhui
Cheng, Shaobing
Xie, Haiyang
Zhou, Lin
Wu, Jian
Zheng, Shusen
author_facet Xiao, Heng
Tong, Rongliang
Ding, Chaofeng
Lv, Zhen
Du, Chengli
Peng, Chuanhui
Cheng, Shaobing
Xie, Haiyang
Zhou, Lin
Wu, Jian
Zheng, Shusen
author_sort Xiao, Heng
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most deadly cancers. Using mRNA microarray analysis, we found that H2AX decreased under hypoxic conditions. Hypoxia is an important physiological and pathological stress that induces H2AX phosphorylation (γ-H2AX), but the regulatory mechanism of γ-H2AX remains elusive in the progress of HCC. We report here that increased γ-H2AX expression in HCC is associated with tumor size, vascular invasion, TNM stage and reduced survival rate after liver transplantation (LT). γ-H2AX knockdown was able to effectively inhibit VEGF expression in vitro and tumorigenicity and angiogenesis of HCC in vivo. The mechanism of γ-H2AX on the angiogenic activity of HCC might go through EGFR/HIF-1α/VEGF pathways under hypoxic conditions. Combined γ-H2AX, HIF-1α and EGFR has better prognostic value for HCC after LT. This study suggests that γ-H2AX is associated with angiogenesis of HCC and γ-H2AX or a combination of γ-H2AX/EGFR/HIF-1α is a novel marker in the prognosis of HCC after LT and a potential therapeutic target.
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spelling pubmed-43858442015-04-14 γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition Xiao, Heng Tong, Rongliang Ding, Chaofeng Lv, Zhen Du, Chengli Peng, Chuanhui Cheng, Shaobing Xie, Haiyang Zhou, Lin Wu, Jian Zheng, Shusen Oncotarget Research Paper Hepatocellular carcinoma (HCC) is one of the most deadly cancers. Using mRNA microarray analysis, we found that H2AX decreased under hypoxic conditions. Hypoxia is an important physiological and pathological stress that induces H2AX phosphorylation (γ-H2AX), but the regulatory mechanism of γ-H2AX remains elusive in the progress of HCC. We report here that increased γ-H2AX expression in HCC is associated with tumor size, vascular invasion, TNM stage and reduced survival rate after liver transplantation (LT). γ-H2AX knockdown was able to effectively inhibit VEGF expression in vitro and tumorigenicity and angiogenesis of HCC in vivo. The mechanism of γ-H2AX on the angiogenic activity of HCC might go through EGFR/HIF-1α/VEGF pathways under hypoxic conditions. Combined γ-H2AX, HIF-1α and EGFR has better prognostic value for HCC after LT. This study suggests that γ-H2AX is associated with angiogenesis of HCC and γ-H2AX or a combination of γ-H2AX/EGFR/HIF-1α is a novel marker in the prognosis of HCC after LT and a potential therapeutic target. Impact Journals LLC 2014-12-10 /pmc/articles/PMC4385844/ /pubmed/25537504 Text en Copyright: © 2015 Xiao 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
Xiao, Heng
Tong, Rongliang
Ding, Chaofeng
Lv, Zhen
Du, Chengli
Peng, Chuanhui
Cheng, Shaobing
Xie, Haiyang
Zhou, Lin
Wu, Jian
Zheng, Shusen
γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition
title γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition
title_full γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition
title_fullStr γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition
title_full_unstemmed γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition
title_short γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition
title_sort γ-h2ax promotes hepatocellular carcinoma angiogenesis via egfr/hif-1α/vegf pathways under hypoxic condition
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385844/
https://www.ncbi.nlm.nih.gov/pubmed/25537504
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