Type

Journal Article

Authors

Cormac T. Taylor
Eoin P. Cummins
Murtaza M. Tambuwala
Martin O Leonard
David A Simpson
Carsten C. Scholz
Alex Cheong
Susan F. Fitzpatrick
Zoltán Neufeld
Luca Cerone
and 1 others

Subjects

Biochemistry

Topics
fibroblasts caco 2 cells humans cytology physiology models biological micrornas animals cell hypoxia genetics microarray analysis metabolism hypoxia inducible factor 1 alpha subunit mice cells cultured mirn155 microrna human mirn155 microrna mouse

MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. (2011)

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 hypoxia-inducible 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-1α 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-1α-dependent transcription.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Cormac T. Taylor, Eoin P. Cummins, Murtaza M. Tambuwala, Martin O Leonard, David A Simpson, Carsten C. Scholz, Alex Cheong, Susan F. Fitzpatrick, Zoltán Neufeld, Luca Cerone and 1 others

Experts in our system

1
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
2
Eoin P. Cummins
University College Dublin
Total Publications: 53
 
3
Murtaza M. Tambuwala
University College Dublin
Total Publications: 12
 
4
Carsten C Scholz
University College Dublin
Total Publications: 21
 
5
Alex Cheong
University College Dublin
Total Publications: 18
 
6
Susan F. Fitzpatrick
University College Dublin
Total Publications: 9
 
7
Zoltán Neufeld
University College Dublin
Total Publications: 17