MicroRNA-206 Protects against Myocardial Ischaemia-Reperfusion Injury in Rats by Targeting Gadd45β

Mol Cells. 2017 Dec 31;40(12):916-924. doi: 10.14348/molcells.2017.0164. Epub 2017 Dec 14.

Abstract

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that Gadd45β (growth arrest DNA damage-inducible gene 45β) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of Gadd45β. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting Gadd45β.

Keywords: Gadd45β; apoptosis; cardiomyocyte; ischaemia–reperfusion; miR-206.

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / metabolism
  • Disease Models, Animal
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / prevention & control*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antigens, Differentiation
  • Gadd45b protein, rat
  • MicroRNAs
  • mirn206 microRNA, rat