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

Boshi Yu1, Mengmeng Li1, Shu Ping Han1

  • 1Department of Pediatrics, Women's Hospital of Nanjing Medical University Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China.

Molecular Medicine Reports
|October 19, 2021
PubMed

Insights

Hsa_circ_105039, underexpressed in congenital heart disease (CHD), promotes cardiomyocyte differentiation and viability. It acts as a sponge for miR-17, targeting cyclinD2, offering a protective effect in iPS cell-derived cardiomyocytes.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Biology
  • Molecular Medicine

Background:

  • Hsa_circ_105039 is underexpressed in congenital heart disease (CHD) patient heart tissue.
  • The precise function and molecular mechanisms of hsa_circ_105039 in CHD remain largely unknown.

Purpose of the Study:

  • To investigate the role and mechanism of hsa_circ_105039 in the context of CHD using induced pluripotent stem (iPS) cell-derived cardiomyocytes.
  • To explore the potential of hsa_circ_105039 as a diagnostic marker for CHD.

Main Methods:

  • Induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes using dimethyl sulfoxide (DMSO).
  • Hsa_circ_105039 knockdown and overexpression were performed to assess effects on cell differentiation, viability, migration, and apoptosis.
  • Luciferase reporter assays were used to identify microRNA (miR) interactions.
  • Reverse transcription-quantitative PCR and western blotting were employed to analyze gene and protein expression.

Main Results:

  • Hsa_circ_105039 overexpression enhanced cardiomyocyte differentiation, viability, and migration while reducing apoptosis.
  • Hsa_circ_105039 functions as a molecular sponge for miR-17, with cyclinD2 identified as a direct target of miR-17.
  • Hsa_circ_105039 upregulated differentiation-related genes and proteins, including natriuretic peptide A, cardiac troponin I, GATA-binding protein 4, and a homobox transcription factor.

Conclusions:

  • Hsa_circ_105039 exerts a protective effect in DMSO-induced iPS cell-derived cardiomyocytes by promoting the miR-17/cyclinD2 pathway.
  • Hsa_circ_105039 represents a potential key molecule for the diagnosis of congenital heart disease.

Keywords:
circular RNAcongenital heart diseasemicroRNA‑17

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