Circular RNA hsa_circ_105039 promotes cardiomyocyte differentiation by sponging miR‑17 to regulate cyclinD2 expression

Mol Med Rep. 2021 Dec;24(6):861. doi: 10.3892/mmr.2021.12501. Epub 2021 Oct 19.

Abstract

Previously it was found that hsa_circ_105039 was underexpressed in the heart tissue of patients with congenital heart disease (CHD). However, the function and mechanism of hsa_circ_105039 in CHD are unclear. In the present study, induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes using 1% dimethyl sulfoxide (DMSO). Cell differentiation, viability, migration and apoptosis were measured before and following hsa_circ_105039 knockdown or overexpression. The results indicated that hsa_circ_105039 overexpression promoted cell differentiation, viability and migration; whereas apoptosis was simultaneously repressed. A luciferase reporter assay verified that hsa_circ_105039 acted as a sponge for microRNA (miR)‑17 and that cyclinD2 was a direct target of miR‑17. Furthermore, differentiation‑related genes and proteins were analyzed by reverse transcription‑quantitative PCR and western blotting, respectively. The results showed that hsa_circ_105039 could also upregulate the expression of differentiation‑related genes and proteins, including natriuretic peptide A, cardiac troponin I, GATA‑binding protein 4 and homobox transcription factor, in iPS cells. The results suggested that hsa_circ_105039 exerted a protective effect by promoting miR‑17/cyclinD2 in DMSO‑induced iPS cardiomyocytes, which indicated that hsa_circ_105039 is a potential key molecule for the diagnosis of CHD.

Keywords: circular RNA; congenital heart disease; microRNA‑17.

MeSH terms

  • Apoptosis / genetics
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Cyclin D2 / genetics
  • Cyclin D2 / metabolism*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / metabolism*
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism*

Substances

  • CCND2 protein, human
  • Cyclin D2
  • MIRN17 microRNA, human
  • MicroRNAs
  • RNA, Circular