The circular RNA hsa_circ_0007623 acts as a sponge of microRNA-297 and promotes cardiac repair

Biochem Biophys Res Commun. 2020 Mar 19;523(4):993-1000. doi: 10.1016/j.bbrc.2019.12.116. Epub 2020 Jan 20.

Abstract

Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs have attracted increasing interest in recent years. However, the mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases, particularly myocardial ischemia, is rarely reported. In the present study, we examined a circular RNA, hsa_circ_0007623, which is highly expressed in hypoxia-induced human umbilical vein endothelial cells (HUVECs) and can act as a sponge for miR-297, which is involved in cardiac repair after acute myocardial ischemia. In hypoxia-stimulated HUVECs, the inhibition of hsa_circ_0007623 expression was found to reduce cell proliferation, migration, and angiogenesis. Further in vivo experiments confirmed the cardioprotective effect of hsa_circ_0007623 expression in isoproterenol-induced acute ischemia mice. Bioinformatics analysis predicted hsa_circ_0007623, sponge miR-297 and miR-297 directly target VEGFA, which was validated by dual-luciferase assay. Subsequently, functional experiments revealed hsa_circ_0007623 silencing could up-regulate miR-297 and down-regulate VEGFA expression, and reduce cell proliferation, migration, and angiogenesis. We concluded that hsa_circ_0007623 can bind to miR-297, promote cardiac repair after acute myocardial ischemia, and protect cardiac function.

Keywords: Acute myocardial ischemia; Circular RNA; Heart repair; miR-297.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cardiomyopathies / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Isoproterenol
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Neovascularization, Physiologic / genetics
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Regeneration*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • MIRN297 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Vascular Endothelial Growth Factor A
  • Isoproterenol