miR-140-5p regulates vascular smooth muscle cell viability, migration and apoptosis by targeting ROBO4 gene expression in atherosclerosis

Luo,Yi; Li,Yangmin; Peng,Hong; Zhao,Yu

doi:10.3892/mmr.2021.11852

miR-140-5p regulates vascular smooth muscle cell viability, migration and apoptosis by targeting ROBO4 gene expression in atherosclerosis

Authors:
- Yi Luo
- Yangmin Li
- Hong Peng
- Yu Zhao
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Affiliations: Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Department of Gynecology, Jialing Branch of Nanchong Central Hospital, Nanchong, Sichuan 637919, P.R. China, Department of Anorectal, Nanchong Central Hospital, Nanchong, Sichuan 637000, P.R. China
Published online on: January 19, 2021 https://doi.org/10.3892/mmr.2021.11852
Article Number: 213
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRs) are essential regulators of atherosclerosis (AS) development; however, the pathogenic roles of miR-140-5p during AS development are not completely understood. The present study investigated the effects of miR‑140-5p on human vascular smooth muscle cells (VSMCs) and its target gene. miR-140-5p and roundabout guidance receptor 4 (ROBO4) mRNA expression levels were determined by performing reverse transcription-quantitative PCR. ROBO4 protein expression levels were analyzed via western blotting. Cell viability, migration, invasion and apoptosis were evaluated by conducting Cell Counting Kit-8, Transwell and flow cytometry assays, respectively. The binding of miR-140-5p to ROBO4 mRNA was verified using the dual-luciferase reporter assay. miR-140-5p was highly expressed in the plaque-containing artery tissues of patients with AS compared with healthy control tissues. Oxidized-low density lipoprotein (ox-LDL) treatment increased miR-140-5p expression and decreased ROBO4 expression in human VSMCs, which promoted VSMC viability, migration and invasion, but suppressed apoptosis compared with the control group. The effects of ox-LDL treatment on VSMCs were attenuated by miR-140-5p inhibitor. miR-140-5p directly bound to the 3'-untranslated region of ROBO4 mRNA. ROBO4 overexpression mitigated the effects of ox-LDL treatment on VSMC viability, migration, invasion and apoptosis. Therefore, the present study suggested that high level miR-140-5p expression promoted VSMC viability, migration, and invasion, and suppressed VSMC apoptosis by reducing ROBO4 gene expression. The present study provided novel insights into AS pathogenesis that may aid the development of new strategies for the treatment and prevention of AS.

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