C-MYC ameliorates ventricular remodeling of myocardial infarction rats via binding to the promoter of microRNA-29a-3p to facilitate TET2 expression

Int J Cardiol. 2022 Jun 15:357:105-112. doi: 10.1016/j.ijcard.2022.01.020. Epub 2022 Jan 10.

Abstract

Background: There is increasing evidence identifying the role of c-MYC in myocardial infarction (MI). Thus, our aim was to discuss the impact of c-MYC/microRNA (miR)-29a-3p/ten-eleven translocation-2 (TET2) axis on MI.

Methods: Sprague-Dawley rats received injections of recombinant adenoviruses at myocardial sites that interfered with c-MYC or miR-29a-3p expression. At 3 days after adenoviral injection, the rats were subjected to myocardial ischemia and reperfusion. Cardiac function, infarct size, cellular death, inflammatory response, oxidative stress, collagen deposition, c-MYC, TET2 and miR-29a-3p expression were analyzed. The interaction between c-MYC and miR-29a-3p as well as that between TET2 and miR-29a-3p was verified.

Results: miR-29a-3p expression was enhanced while c-MYC and TET2 expression was decreased in the myocardial tissue of MI rats. Up-regulating c-MYC or down-regulating miR-29a-3p in MI rat hearts improved cardiac function and reduced infarct size and myocardial apoptotic death, restrained oxidative stress, inflammatory response, attenuated collagen deposition. c-Myc bound to the promoter of miR-29a-3p and repressed miR-29a-3p expression. TET2 was a target of miR-29a-3p.

Conclusion: Our study provides evidence that c-MYC binding to the promoter of miR-29a-3p to facilitate TET2 expression has therapeutic effect on ventricular remodeling of MI rats.

Keywords: C-MYC; Collagen; Myocardial infarction; Promoter; Ten-eleven translocation-2; Ventricular remodeling; microRNA-29a-3p.

MeSH terms

  • Animals
  • Collagen
  • DNA-Binding Proteins / genetics
  • Dioxygenases*
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Myocardial Infarction*
  • Proto-Oncogene Proteins c-myc
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Remodeling

Substances

  • DNA-Binding Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • Collagen
  • Dioxygenases