MicroRNA-7a/b protects against cardiac myocyte injury in ischemia/reperfusion by targeting poly(ADP-ribose) polymerase

PLoS One. 2014 Mar 3;9(3):e90096. doi: 10.1371/journal.pone.0090096. eCollection 2014.

Abstract

Objectives: MicroRNA-7 (miR-7) is highly connected to cancerous cell proliferation and metastasis. It is also involved in myocardial ischemia-reperfusion (I/R) injury and is upregulated in cardiomyocyte under simulated I/R (SI/R). We aimed to investigate the role of miR-7 during myocardial I/R injury in vitro and in vivo and a possible gene target.

Methods and results: Real-time PCR revealed that miR-7a/b expression was upregulated in H9c2 cells after SI/R. Flow cytometry showed SI/R-induced cell apoptosis was decreased with miR-7a/b mimic transfection but increased with miR-7a/b inhibitor in H9c2 cells. In a rat cardiac I/R injury model, infarct size determination and TUNEL assay revealed that miR-7a/b mimic decreased but miR-7a/b inhibitor increased cardiac infarct size and cardiomyocyte apoptosis as compared with controls. We previously identified an important gene connected with cell apoptosis--poly(ADP-ribose) polymerase (PARP)--as a candidate target for miR-7a/b and verified the target by luciferase reporter activity assay and western blot analysis.

Conclusions: miR-7a/b is sensitive to I/R injury and protects myocardial cells against I/R-induced apoptosis by negatively regulating PARP expression in vivo and in vitro. miR-7a/b may provide a new therapeutic approach for treatment of myocardial I/R injury. Poly(ADP-ribose) polymerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Base Sequence
  • Cell Line
  • Humans
  • In Situ Nick-End Labeling
  • MicroRNAs / physiology*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / pathology*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Rats
  • Reperfusion Injury / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MIRN7 microRNA, human
  • MicroRNAs
  • Poly(ADP-ribose) Polymerases

Grants and funding

This work was supported by the the National Natural Science Foundation of China [81070087], and the National 973 Basic Research Program of China [2012CB722406].the URL of any funder's website:http://isisn.nsfc.gov.cn/egrantweb/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.