The microRNA-210/Casp8ap2 Axis Alleviates Hypoxia-Induced Myocardial Injury by Regulating Apoptosis and Autophagy

Cytogenet Genome Res. 2021;161(3-4):132-142. doi: 10.1159/000512254. Epub 2021 Apr 21.

Abstract

Coronary heart disease (CHD) is a serious condition comprising atherosclerosis-mediated ischaemic and hypoxic myocardial injury. This study aimed to investigate the mechanism of the miR-210/Casp8ap2 signalling pathway in hypoxic myocardial cells. mRNA and protein expression levels were determined by quantitative real-time PCR and western blotting, respectively. MTT was used to evaluate cell survival, and flow cytometry was used to assess apoptosis and the cell cycle distribution. The interaction between miR-210 and -Casp8ap2 was detected by dual-luciferase reporter assay. As a result, overexpression of miR-210 significantly inhibited apoptosis and reduced the proportion of cells in G1 phase. Moreover, miR-210 suppressed autophagy by upregulating p62 levels and reducing the LC3-II/I ratio in hypoxic cardiomyocytes. miR-210 regulated apoptosis and autophagy by directly targeting Casp8ap2. Furthermore, the expression levels of Casp8ap2, Cleaved caspase 8, Cleaved caspase 3and Beclin-1 were all decreased in response to miR-210. In short, our results suggest that miR-210 exerts anti-apoptotic and anti-autophagic effects in hypoxic cardiomyocytes, which alleviates myocardial injury in response to hypoxia.

Keywords: Apoptosis; Casp8ap2; Hypoxia; Myocardial injury; miR-210.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / genetics*
  • Base Sequence
  • Blotting, Western
  • Cell Hypoxia
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • MicroRNAs / genetics*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / genetics*

Substances

  • Apoptosis Regulatory Proteins
  • CASP8AP2 protein, rat
  • MIRN210 microRNA, rat
  • MicroRNAs