miR-124-3p downregulates EGR1 to suppress ischemia-hypoxia reperfusion injury in human iPS cell-derived cardiomyocytes

Sci Rep. 2024 Jun 27;14(1):14811. doi: 10.1038/s41598-024-65373-x.

Abstract

Ischemic heart diseases are a major global cause of death, and despite timely revascularization, heart failure due to ischemia-hypoxia reperfusion (IH/R) injury remains a concern. The study focused on the role of Early Growth Response 1 (EGR1) in IH/R-induced apoptosis in human cardiomyocytes (CMs). Human induced pluripotent stem cell (hiPSC)-derived CMs were cultured under IH/R conditions, revealing higher EGR1 expression in the IH/R group through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). Immunofluorescence analysis (IFA) showed an increased ratio of cleaved Caspase-3-positive apoptotic cells in the IH/R group. Using siRNA for EGR1 successfully downregulated EGR1, suppressing cleaved Caspase-3-positive apoptotic cell ratio. Bioinformatic analysis indicated that EGR1 is a plausible target of miR-124-3p under IH/R conditions. The miR-124-3p mimic, predicted to antagonize EGR1 mRNA, downregulated EGR1 under IH/R conditions in qRT-PCR and WB, as confirmed by IFA. The suppression of EGR1 by the miR-124-3p mimic subsequently reduced CM apoptosis. The study suggests that treatment with miR-124-3p targeting EGR1 could be a potential novel therapeutic approach for cardioprotection in ischemic heart diseases in the future.

MeSH terms

  • Apoptosis*
  • Down-Regulation*
  • Early Growth Response Protein 1* / genetics
  • Early Growth Response Protein 1* / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocytes, Cardiac* / metabolism

Substances

  • MicroRNAs
  • Early Growth Response Protein 1
  • MIRN124 microRNA, human
  • EGR1 protein, human