Author:
Wang Weitie,Wang Yong,Piao Hulin,Li Bo,Zhu Zhicheng,Li Dan,Wang Tiance,Liu Kexiang
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.
Subject
Genetics (clinical),Genetics,Molecular Medicine
Cited by
8 articles.
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