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Downregulation of miR-122 attenuates hypoxia/reoxygenation (H/R)-induced myocardial cell apoptosis by upregulating GATA-4.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2016 Sep 23; Vol. 478 (3), pp. 1416-22. Date of Electronic Publication: 2016 Aug 25. - Publication Year :
- 2016
-
Abstract
- MicroRNA-122 has been reported to play a potential role in the apoptosis of myocardial cells. However, the effect of miR-122 in regulating myocardial ischemic injury has not been previously addressed. This study aimed to investigate the effect and the molecular basis of miR-122 on myocardial ischemic injury. Using the hypoxia/reoxygenation (H/R) model of rat cardiomyocytes H9C2 in vitro, we found that miR-122 was highly expressed in H9C2 cells after H/R treatment. Overexpression of miR-122 by recombinant adeno-associated viral vector infection markedly promoted the apoptosis of H9C2 cells induced by H/R treatment, whereas miR-122 inhibition significantly decreased cell apoptosis. Dual-luciferase reporter assay and western blot assay revealed that GATA-4 was a direct target gene of miR-122, and miR-122 suppressed the expression of GATA-4 via binding to its 3'-UTR. We further identified that overexpression of miR-122 inhibited the expression of GATA-4 at the mRNA and protein levels, whereas the inhibition of miR-122 upregulated the expression of GATA-4. Moreover, GATA-4 was poorly expressed in H/R H9C2 cells and the apoptosis induced by H/R was associated with the decrease in GATA-4 expression. Importantly, silencing of GATA-4 apparently abrogated the inhibitory effect of anti-miR-122 on H/R-induced cell apoptosis. In conclusion, these findings indicate that downregulation of miR-122 alleviates cardiomyocyte H/R injury through upregulation of GATA-4 expression, supplying a novel molecular target for myocardial ischemic injury.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis genetics
Base Sequence
Cell Hypoxia drug effects
Cell Hypoxia genetics
Cell Line
Down-Regulation genetics
GATA4 Transcription Factor metabolism
HEK293 Cells
Humans
MicroRNAs metabolism
Myocardium metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Up-Regulation drug effects
Apoptosis drug effects
Down-Regulation drug effects
GATA4 Transcription Factor genetics
MicroRNAs genetics
Myocardium pathology
Oxygen pharmacology
Up-Regulation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 478
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 27569279
- Full Text :
- https://doi.org/10.1016/j.bbrc.2016.08.139