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Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro

MIAO Rui-zheng LIU Li-qing CHEN Li LI Zhang LI Le-ping GUO Ren-le LI Jian-feng GUO Xiao-bo

中华医学杂志(英文版)Issue(7):1310-1315,6.
中华医学杂志(英文版)Issue(7):1310-1315,6.DOI:10.3760/cma.j.issn.0366-6999.2012.07.022

Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro

Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro

MIAO Rui-zheng 1LIU Li-qing 1CHEN Li 1LI Zhang 1LI Le-ping 1GUO Ren-le 1LI Jian-feng 2GUO Xiao-bo1

作者信息

  • 1. Department of Surgery Shandong Provincial Hospital, Affiliated to Shandong University, Jinan,Shandong 250021, China
  • 2. Central Laboratory , Shandong Provincial Hospital, Affiliated to Shandong University, Jinan,Shandong 250021, China
  • 折叠

摘要

Abstract

Background One effect of solid tumors is severe hypoxia of local tissues.Heme oxygenase-1 (HO-1) is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors.Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation.However,whether and how changes in HO-1 activity affect -HlF-1 gene expression has not been reported previously.Methods Hypoxia-inducible models were established using gastric cancer cell lines (SGC-7901) in a hypoxia incubator.Cells were placed in four groups:Group A,transfected by plasmid harboring HO-1 shRNA; Group B,transfected with scrambled shRNA vector; Group C,treated with hemin; and Group D,exposed to hypoxia only.Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction.Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting.Results mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A (P <0.01),but lower than in Group C (P <0.01).Chromatin immunoprecipitation analysis showed that HlF-1 was identified as the direct HO-1 target gene.Conclusion While affected by HIF-1,HO-1 up-regulation promotes the expression of HlF-1 and the down-regulation of HO-1 suppresses the expression of HlF-1 gene.

关键词

heme oxygenase-1/hypoxia inducible factor- 1/expression/RNA interference

Key words

heme oxygenase-1/hypoxia inducible factor- 1/expression/RNA interference

引用本文复制引用

MIAO Rui-zheng,LIU Li-qing,CHEN Li,LI Zhang,LI Le-ping,GUO Ren-le,LI Jian-feng,GUO Xiao-bo..Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro[J].中华医学杂志(英文版),2012,(7):1310-1315,6.

基金项目

This study was supported by the Natural Science Fund of Shandong Province,China (No.Y2007C127),the Natural Science Foundation of Shandong Province of China (No.ZR2011HM041),the Key Research Project from Shandong Science and Technology Commission (No.2011GGB14158) and the National Youthful Science Foundation of China (No.81101858). (No.Y2007C127)

中华医学杂志(英文版)

OACSCDCSTPCDMEDLINESCI

0366-6999

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