Critical functions of microRNA-30a-5p-E2F3 in cardiomyocyte apoptosis induced by hypoxia/reoxygenation

Kaohsiung J Med Sci. 2021 Feb;37(2):92-100. doi: 10.1002/kjm2.12309. Epub 2020 Oct 15.

Abstract

The high-mortality rate of cardiovascular diseases (CVDs) is associated with the myocardial ischemia and reperfusion (I/R). Recent investigations have revealed that microRNAs (miRNAs) exert vital functions in the apoptosis of cardiomyocyte cell. Nevertheless, the potential role of miR-30a-5p in the regulation of cardiomyocyte cell apoptosis needs to be illuminated. In the current study, we observed that hypoxia/reoxygenation (H/R) remarkably raised the level of miR-30a-5p but reduced the expression of E2F transcription factor 3 (E2F3) in H9c2 cardiomyocytes. In vivo, miR-30a-5p was found to be significantly upregulated in the hearts of rats following I/R. Downregulation of miR-30a-5p using anti-miR-30a-5p decreased H9c2 cardiomyocytes apoptosis caused by H/R and promoted the proliferation of H9c2 inhibited by H/R. Moreover, E2F3 was a possible target gene of miR-30a-5p and upregulation of miR-30a-5p reduced the expression level of E2F3 in H9c2 cardiomyocytes. We further identified that E2F3 silencing reversed the effect of anti-miR-30a-5p on the proliferation and apoptosis in H/R treated H9c2 cells. These studies suggested that downregulation of miR-30a-5p attenuated the impact of H/R on H9c2 cardiomyocytes through targeting E2F3.

Keywords: E2F3; apoptosis; hypoxia/reoxygenation; miR-30a-5p.

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Base Sequence
  • Cell Hypoxia / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • E2F3 Transcription Factor / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / cytology*
  • Oxygen / metabolism*
  • Rats
  • Up-Regulation / genetics

Substances

  • E2F3 Transcription Factor
  • MIRN30 microRNA, rat
  • MicroRNAs
  • Oxygen