MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch

Cao,Yushi; Cao,Zhongwen; Wang,Weitie; Jie,Xiangyu; Li,Lei

doi:10.3892/mmr.2021.12266

MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch

Authors:
- Yushi Cao
- Zhongwen Cao
- Weitie Wang
- Xiangyu Jie
- Lei Li
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Affiliations: Department of Hepatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Vascular Surgery, Qianwei Hospital of Jilin Province, Changchun, Jilin 130012, P.R. China, Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: July 1, 2021 https://doi.org/10.3892/mmr.2021.12266
Article Number: 627
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Varicose veins are among the most common disorders of the vascular system; however, the pathogenesis of varicose veins remains unclear. The present study aimed to investigate the roles of microRNA (miR)‑199a‑5p in varicose veins and in the phenotypic transition of vascular smooth muscle cells (VSMCs). Bioinformatics analysis confirmed that miR‑199a‑5p had target sites on the forkhead box C2 (FOXC2) 3'‑untranslated region. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting were used to detect the expression levels of miR‑199a‑5p and FOXC2 in varicose vein and normal great saphenous vein tissues. Cell Counting Kit‑8 and Transwell migration assays were performed to validate the effects of miR‑199a‑5p on VSMCs. Contractile markers, such as smooth muscle 22α, calponin, smooth muscle actin and myosin heavy chain 11 were used to detect phenotypic transition. RT‑qPCR revealed that miR‑199a‑5p was downregulated in varicose veins compared with expression in normal great saphenous veins, whereas FOXC2 was upregulated in varicose veins. In addition, biomarkers of the VSMC contractile phenotype were downregulated in varicose veins. Overexpression of miR‑199a‑5p by mimics suppressed VSMC proliferation and migration, whereas depletion of miR‑199a‑5p enhanced VSMC proliferation and migration. Notably, the effects caused by miR‑199a‑5p could be reversed by FOXC2 overexpression. Dual luciferase reporter analysis confirmed that FOXC2 was a target of miR‑199a‑5p. In conclusion, miR‑199a‑5p may be a novel regulator of phenotypic switching in VSMCs by targeting FOXC2 during varicose vein formation.

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