Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells.

Weitie Wang,Tiance Wang,Zhicheng Zhu,Kexiang Liu,Bo Li,Dan Li,Hulin Piao,Yong Wang

doi:10.3389/fgene.2020.572707

Weitie Wang, Tiance Wang + Show 6 more

Open Access

https://doi.org/10.3389/fgene.2020.572707

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Abstract

Aortic dissection (AD) is among the most fatal cardiovascular diseases. However, the pathogenesis of AD remains poorly understood. This study aims to integrate the microRNAs (miRNA) and mRNA profiles and use bioinformatics analyses with techniques in molecular biology to delineate the potential mechanisms involved in the development of AD. We used the human miRNA and mRNA microarray datasets GSE98770, GSE52093, and GEO2R, Venn diagram analysis, gene ontology, and protein–protein interaction networks to identify target miRNAs and mRNAs involved in AD. RNA interference, western blotting, and luciferase reporter assays were performed to validate the candidate miRNAs and mRNAs in AD tissues and human vascular smooth muscle cells (VSMCs). Furthermore, we studied vascular smooth muscle contraction in AD. In silico analyses revealed that miR-193a-3p and ACTG2 were key players in the pathogenesis of AD. miR-193a-3p was upregulated in the AD tissues. We also found that biomarkers for the contractile phenotype in VSMCs were downregulated in AD tissues. Overexpression and depletion of miR-193a-3p enhanced and suppressed VSMC proliferation and migration, respectively. Dual luciferase reporter assays confirmed that ACTG2 was a target of miR-193a-3p. ACTG2 was also downregulated in human AD tissues and VMSCs overexpressing miR-193a-3p. Taken together, miR-193a-3p may be a novel regulator of phenotypic switching in VSMCs and the miR-193a-3p/ACTG2 axis may serve as a promising diagnostic biomarker and therapeutic candidate for AD.

Highlights

Type A aortic dissection (AD) is a fatal cardiovascular disease associated with high morbidity and mortality, and requires a complex treatment regimen (Elsayed et al, 2017; Silaschi et al, 2017)
Vascular smooth muscle cells in aortic media maintain the biological properties of the aortic wall (Rzucidlo et al, 2007; Ren et al, 2017; Chen et al, 2019; Wang et al, 2019b)
Proliferation and migration of Vascular smooth muscle cells (VSMCs) are regulated by phenotypic switching and correlate with the initial stages involved in the development of AD (An et al, 2017a,b; Li et al, 2018; Zhang and Wang, 2019)

Summary

Introduction

Type A aortic dissection (AD) is a fatal cardiovascular disease associated with high morbidity and mortality, and requires a complex treatment regimen (Elsayed et al, 2017; Silaschi et al, 2017). Vascular smooth muscle cells (VSMCs) are involved in vascular function and have been implicated in the pathogenesis of AD (Zhang et al, 2016; Wei et al, 2017). The precise mechanisms involved in AD remain to be fully understood. It is important to delineate the roles of VSMCs in AD and phenotypic plasticity. This will help identify new modes of treatment, especially targeted drug therapy. Bioinformatics tools can analyze such high-throughput data, while omitting “junk” data to provide reliable analyses

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