LncRNA Gm4419 Regulates Myocardial Ischemia/Reperfusion Injury Through Targeting the miR-682/TRAF3 Axis

J Cardiovasc Pharmacol. 2020 Sep;76(3):305-312. doi: 10.1097/FJC.0000000000000867.

Abstract

Myocardial cell death during acute myocardial infarction occurs because of acute ischemia, persistent ischemia, reperfusion-associated injury, and the inflammatory infiltrate as a response to cell necrosis. In the present study, quantitative real-time PCR showed that lncRNA Gm4419 was highly upregulated in ischemia/reperfusion myocardial tissues and hypoxia/reoxygenation H9C2 cells, whereas miR-682 was downregulated. Knocking down Gm4419 with sh-Gm4419 resulted in the rescue of myocardial infarction and apoptosis induced by ischemia/reperfusion or hypoxia/reoxygenation. Our study further demonstrated that Gm4419 may bind with miR-682 directly. Moreover, in vitro experiments further demonstrated that miR-682 could bind to tumor necrosis factor receptor-associated factor 3 (TRAF3) directly. Most importantly, TRAF3 overexpression could counteract the effect of sh-Gm4419. Taken together, our study indicated that Gm4419 may target miR-682 via sponging to increase TRAF3 expression, thereby contributing to myocardial I/R injury. Therefore, the Gm4419/miR-682/TRAF3 axis may be an important regulatory mechanism in myocardial ischemia/reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Inflammation Mediators / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats, Sprague-Dawley
  • Signal Transduction
  • TNF Receptor-Associated Factor 3 / genetics
  • TNF Receptor-Associated Factor 3 / metabolism*

Substances

  • Cytokines
  • Inflammation Mediators
  • MIRN682 microRNA, rat
  • MicroRNAs
  • RNA, Long Noncoding
  • TNF Receptor-Associated Factor 3