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

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.

• Authors: Wang Xing, Tiangang Li, Yixuan Wang, Yi Qiang, Chencheng Ai, Hanbo Tang
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 41 Issue 5 Pg. 476-487 (Oct 2021) ISSN: 1532-4281 [Electronic] England
• PMID: 33054489 (Publication Type: Journal Article)

Chemical References

• MIRN33a microRNA, human
• Membrane Proteins
• MicroRNAs
• NOMO1 protein, human

Topics

• Apoptosis
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Gene Expression Regulation
• Humans
• Membrane Proteins (genetics, metabolism)
• MicroRNAs (genetics)
• Myocytes, Cardiac (cytology, metabolism)
• Stem Cells (cytology, metabolism)