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 dualluciferase 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.

Role and mechanism of miRNA in cardiac microvascular endothelial cells in cardiovascular diseases

“…MiRNA-33a-5p is an intron miRNA that is located inside the intron sequence of the sterol-response-element-binding protein gene 2 (SREBP2) ( 63 ). The study has shown that miR-33a-5p promotes apoptosis via targeting nodal modulator1 (NOMO1) and other targets ( 64 ). After treatment with Hcy in the CMEC vascular dysfunction model, growth-arrest specific transcript 5 (GAS5) expression is markedly reduced whereas miRNA-33a-5p expression is elevated ( 65 ).…”

KLF14/miR‐1283/TFAP2C axis inhibits HER2‐positive breast cancer progression via declining tumor cell proliferation

“…Abundant literature has confirmed the crucial role of miRNAs in the pathogenesis of human cancers, including breast cancer 9–11 . By targeting different molecules, miRNAs are capable to regulate various biological processes, including cell proliferation and apoptosis 12,13 . Research has disclosed the inhibitory effect of miR‐1283 in mediating cell proliferation and the facilitating role in the regulation of cell apoptosis in glioma and liver cancer 14,15 .…”

“…[9][10][11] By targeting different molecules, miRNAs are capable to regulate various biological processes, including cell proliferation and apoptosis. 12,13 Research has disclosed the inhibitory effect of miR-1283 in mediating cell proliferation and the facilitating role in the regulation of cell apoptosis in glioma and liver cancer. 14,15 However, to our knowledge, the exact impact of miR-1283 on HER2+ breast cancer remains poorly understood.…”

miRNAs Epigenetic Tuning of Wall Remodeling in the Early Phase after Myocardial Infarction: A Novel Epidrug Approach

“…Conversely, other pathways appear to be regulated only by pro-proliferative or pro-apoptotic miRNAs, such as the NF-kB pathway which can be activated by blockade of the suppressor of cytokine signaling 3 (SOCS3) and the NF-kB inhibitor interacting Ras-like 2 (NKIRAS2) by miR-324 [38] and miR-1180 [39], respectively. However, the Nodal signaling pathway, an important signal transduction pathway active during embryonic heart development [40], is suppressed by miR-33a-5p which targets nodal modulator 1 (NOMO1) [41].…”

“…92, miR-19a/b or miR-221-3p [33][34][35] or silenced by miR-208a and miR-489, which b phosphoinositide 3-kinase (PI3K) and spindlin-1 (SPIN1), respectively [36 Conversely, other pathways appear to be regulated only by pro-proliferative or apoptotic miRNAs, such as the NF-kB pathway which can be activated by blockade o suppressor of cytokine signaling 3 (SOCS3) and the NF-kB inhibitor interacting Ras-l (NKIRAS2) by miR-324 [38] and miR-1180 [39], respectively. However, the Nodal sig ing pathway, an important signal transduction pathway active during embryonic h development [40], is suppressed by miR-33a-5p which targets nodal modulat (NOMO1) [41]. 92, miR-19a/b or miR-221-3p [33][34][35] or silenced by miR-208a and miR-489, which b phosphoinositide 3-kinase (PI3K) and spindlin-1 (SPIN1), respectively [36 Conversely, other pathways appear to be regulated only by pro-proliferative or apoptotic miRNAs, such as the NF-kB pathway which can be activated by blockade of suppressor of cytokine signaling 3 (SOCS3) and the NF-kB inhibitor interacting Ras-li (NKIRAS2) by miR-324 [38] and miR-1180 [39], respectively.…”