1. Academic Validation
  2. MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis

MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis

  • J Recept Signal Transduct Res. 2021 Oct;41(5):476-487. doi: 10.1080/10799893.2020.1825492.
Wang Xing 1 Tiangang Li 2 Yixuan Wang 2 Yi Qiang 1 Chencheng Ai 1 Hanbo Tang 1
Affiliations

Affiliations

  • 1 Cardiovascular Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou City, China.
  • 2 Department of Ultrasonography, Gansu Provincial Maternity and Child-care Hospital, Lanzhou City, China.
Abstract

Purpose: MicroRNA (miRNA) is known to be involved in the pathological process of congenital heart disease (CHD), and nodal modulator1 (NOMO1) is a critical determinant of heart formation. The present study aims to discover the effect of miR-33a-5p and NOMO1 on CHD.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expressions of miR-33a-5p mimic or inhibitor and overexpressed NOMO1 plasmid orNOMO1 knockdown. Human cardiomyocyte progenitor cells (hCMPCs) proliferation was measured by cell counting kit-8 (CCK-8) at 24, 48 and 72 h. Flow cytometry was applied to investigate hCMPCs cell cycle progression and Apoptosis. Expressions of cell apoptotic proteins Bax, Cleaved(C) Caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. Target genes and potential binding sites of NOMO1 and miR-33a-5p were predicted with Targetscan 7.2, and was confirmed through dual-luciferase reporter assay.

Results: Up-regulation of miR-33a-5p inhibited hCMPCs proliferation, cell cycle G0/S transition but promoted hCMPCs Apoptosis, which was partially mitigated by overexpressed NOMO1. NOMO1 was the target gene of miR-33a-5p. Expressions of Bax and C Caspase-3 were enhanced but expressions of Bcl-2, GATA4, cTnT and MEF2C were reduced by up-regulation of miR-33a-5p, which was partially mitigated by overexpressed NOMO1.

Conclusion: Up-regulation of miR-33a-5p inhibited hCMPCs proliferation, cell cycle G0/S transition and differentiation into cardiomyocytes but promoted Apoptosis via targeting NOMO1.

Keywords

Congenital heart disease; human cardiomyocyte progenitor cells; miR-33a-5p; nodal modulator1.

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