MicroRNA-98 attenuates cardiac ischemia-reperfusion injury through inhibiting DAPK1 expression

IUBMB Life. 2019 Feb;71(2):166-176. doi: 10.1002/iub.1879. Epub 2018 Nov 12.

Abstract

Cardiovascular ischemic disease is a large class of diseases that are harmful to human health. The significant role of microRNAs (miRNAs) in terms of controlling cardiac injury has been reported in latest studies. MiR-98 is very important in regulating the apoptosis, the differentiation, the growth as well as the metastasis of cells. Nevertheless, the effect of miR-98 in the cardiac ischemia reperfusion (I/R) injury has rarely been investigated. In the current research, we found that the miR-98 expression was down-regulated in the cardiomyocytes subjected to hypoxia/reoxygenation (H/R) and in the myocardium of the I/R rats. In addition, over-expression of miR-98 could significantly reduce the myocardial oxidative stress and ischemic injury as well as cell apoptosis. In agreement, similar findings were demonstrated in H9c2 cells subjected to H/R injury. Bioinformatic analysis using MiRanda and TargetScan and luciferase activity assay confirmed death-associated protein kinase 1 (DAPK1) as a direct target of miR-98. These findings suggest that miR-98 may be exploited as a novel molecular marker or therapeutic target for myocardial I/R injury. © 2018 IUBMB Life, 71(1):166-176, 2019.

Keywords: DAPK1; hypoxia; ischemia-reperfusion injury; microRNA-98; myocardium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Cell Differentiation / drug effects
  • Cell Hypoxia / genetics
  • Cell Line
  • Death-Associated Protein Kinases / antagonists & inhibitors
  • Death-Associated Protein Kinases / genetics*
  • Death-Associated Protein Kinases / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocardial Reperfusion Injury / genetics*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Oxidative Stress / drug effects
  • Oxygen / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • MIRN98 microRNA-98, rat
  • MicroRNAs
  • Oligoribonucleotides
  • RNA, Small Interfering
  • Dapk1 protein, rat
  • Death-Associated Protein Kinases
  • Oxygen