Inhibition of miR-182-5p attenuates ROS and protects against myocardial ischemia-reperfusion injury by targeting STK17A

Cell Cycle. 2022 Aug;21(15):1639-1650. doi: 10.1080/15384101.2022.2060640. Epub 2022 May 3.

Abstract

Reperfusion therapy for acute myocardial infarction inevitably leads to ischemia-reperfusion (I/R) injury. A number of miRNAs are reported to be involved in I/R injury. This study aims to investigate the role and underlying mechanism of miR-182-5p in I/R injury. An in vivo model of I/R-induced rat myocardial injury and an in vitro model of H/R H9c2 cells were established to investigate the role and mechanism of miR-182-5p in I/R injury. The myocardial infarct size was determined by TTC staining. The serum CK-MB level was determined by ELISA kit. The miR-182-5p inhibitors or mimics were used to down-regulate or up-regulate its expression. The apoptosis and ROS were detected by flow cytometry. The expression of the proteins was detected by western blot. The binding of STK17A and miR-182-5p was validated by dual-luciferase reporter assay. The miR-182-5p was confirmed to be highly expressed in I/R injury rats and H/R H9c2 cells. Inhibition of miR-182-5p significantly reduced the infarct size and decreased the serum CK-MB level of I/R rats, and significantly reduced the ROS level but increased the level of MnSOD and catalase. While, an opposite effect was observed in the miR-182-5p mimics group. Furthermore, our results suggested that miR-182-5p targeted STK17A, and TK17A knockdown significantly increased the apoptotic rate and ROS level. The inhibitory effect of miR-182-5p inhibitors on apoptotic rate, ROS, MnSOD, and catalase levels were abrogated by siSTK17A. These results indicate that miR-182-5p regulates the apoptosis and ROS and protects against myocardial I/R injury by targeting STK17A.

Keywords: MiR-182-5p; ROS; STK17A; apoptosis; myocardial ischemia-reperfusion injury.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins* / genetics
  • Catalase / genetics
  • Catalase / metabolism
  • MicroRNAs* / metabolism
  • Myocardial Infarction* / genetics
  • Myocardial Infarction* / metabolism
  • Myocardial Reperfusion Injury* / genetics
  • Myocardial Reperfusion Injury* / metabolism
  • Myocytes, Cardiac / metabolism
  • Protein Serine-Threonine Kinases* / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • MIRN182 microRNA, rat
  • MicroRNAs
  • Reactive Oxygen Species
  • Catalase
  • Protein Serine-Threonine Kinases

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.