Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro
10.3760/cma.j.issn.0366-6999.2012.07.022
- Author:
Rui-Zheng MIAO
1
;
Li-Qing LIU
;
Li CHEN
;
Zhang LI
;
Le-Ping LI
;
Ren-Le GUO
;
Jian-Feng LI
;
Xiao-Bo GUO
Author Information
1. Department of Surgery Shandong Provincial Hospital, Affiliated to Shandong University, Jinan,Shandong 250021, China
- Keywords:
heme oxygenase-1;
hypoxia inducible factor- 1;
expression;
RNA interference
- From:
Chinese Medical Journal
2012;(7):1310-1315
- CountryChina
- Language:Chinese
-
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.
