MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7.

Abstract

BACKGROUND:

MicroRNAs (miRNAs) regulate a lot of physiological and pathological processes, including myocardial ischemia/reperfusion. Recent studies reported that knockdown of miR-92a could attenuate ischemia/reperfusion-induced myocardial injury. In the present study, we examined the potential anti-apoptotic effects of miR-92a in a rat myocardiocyte cell line, and the possible role of Smad7 in such actions.

METHODOLOGY AND RESULTS:

In a preliminary bioinformatic analysis, we identified SMAD family member 7 (Smad7) as a potential target for miR-92a. A luciferase reporter assay indeed demonstrated that miR-92a could inhibit Smad7 expression. Myocardial ischemia/reperfusion was simulated in rat H9c2 cells with 24-h hypoxia followed by 12-h reoxygenation. Prior to hypoxia/reoxygenation, cells were transfected by miR-92a inhibitor. In some experiments, cells were co-transfected with siRNA-Smad7. The miR-92a inhibitor dramatically reduced the release of lactate dehydrogenase and malonaldehyde, and attenuated cardiomyocyte apoptosis. The miR-92a inhibitor increased SMAD7 protein level and decreased nuclear NF-κB p65 protein. Effects of the miR-92a inhibitor were attenuated by co-transfection with siRNA-Smad7.

CONCLUSION:

Inhibiting miR-92a can attenuate myocardiocyte apoptosis induced by hypoxia/reoxygenation by targeting Smad7.

• Authors: Busheng Zhang, Mi Zhou, Canbo Li, Jingxin Zhou, Haiqing Li, Dan Zhu, Zhe Wang, Anqing Chen, Qiang Zhao
• Journal: PloS one (PLoS One) Vol. 9 Issue 6 Pg. e100298 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24941323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN92 microRNA, rat
• MicroRNAs
• Oligonucleotides
• RNA, Small Interfering
• Rela protein, rat
• Smad7 Protein
• Smad7 protein, rat
• Transcription Factor RelA
• Malondialdehyde
• L-Lactate Dehydrogenase
• Oxygen

Topics

• Animals
• Apoptosis (drug effects)
• Cell Hypoxia
• Cell Line
• Gene Expression Regulation
• L-Lactate Dehydrogenase (metabolism)
• Malondialdehyde (metabolism)
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Models, Biological
• Molecular Mimicry
• Myocardial Reperfusion Injury (genetics, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Oligonucleotides (pharmacology)
• Oxygen (pharmacology)
• RNA, Small Interfering (genetics, metabolism)
• Rats
• Signal Transduction
• Smad7 Protein (antagonists & inhibitors, genetics, metabolism)
• Transcription Factor RelA (antagonists & inhibitors, genetics, metabolism)