MicroRNA promotes resolution of hypoxia-inducible factor activity during prolonged hypoxia in intestinal epithelial cell

Brunig, Ulrike, Cerone, Luca, Neufeld, Zoltan, Simpson, David A., Leonard, Martin O., Tambuwala, Murtaza M., Cummins, Eoin P. and Taylor, Cormac T. (2011) MicroRNA promotes resolution of hypoxia-inducible factor activity during prolonged hypoxia in intestinal epithelial cell. Molecular and Cellular Biology, 31 19: 4087-4096. doi:10.1128/MCB.01276-10

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Author Brunig, Ulrike
Cerone, Luca
Neufeld, Zoltan
Simpson, David A.
Leonard, Martin O.
Tambuwala, Murtaza M.
Cummins, Eoin P.
Taylor, Cormac T.
Title MicroRNA promotes resolution of hypoxia-inducible factor activity during prolonged hypoxia in intestinal epithelial cell
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2011-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1128/MCB.01276-10
Open Access Status File (Publisher version)
Volume 31
Issue 19
Start page 4087
End page 4096
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1α (but not HIF-2α) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxiainducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1α mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1α in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1α mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1α stabilization and activity. Based on these data and a mathematical model of HIF-1 suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1α activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1-α-dependent transcription.
Keyword Biochemistry & Molecular Biology
Cell Biology
Biochemistry & Molecular Biology
Cell Biology
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Mathematics and Physics
Non HERDC
 
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Created: Tue, 31 Jan 2012, 20:23:37 EST by Kay Mackie on behalf of School of Mathematics & Physics