Cargando…
Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells
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 mech...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835941/ https://www.ncbi.nlm.nih.gov/pubmed/33510768 http://dx.doi.org/10.3389/fgene.2020.572707 |
_version_ | 1783642644009713664 |
---|---|
author | Wang, Weitie Wang, Yong Piao, Hulin Li, Bo Zhu, Zhicheng Li, Dan Wang, Tiance Liu, Kexiang |
author_facet | Wang, Weitie Wang, Yong Piao, Hulin Li, Bo Zhu, Zhicheng Li, Dan Wang, Tiance Liu, Kexiang |
author_sort | Wang, Weitie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7835941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78359412021-01-27 Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells Wang, Weitie Wang, Yong Piao, Hulin Li, Bo Zhu, Zhicheng Li, Dan Wang, Tiance Liu, Kexiang Front Genet Genetics 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. Frontiers Media S.A. 2021-01-12 /pmc/articles/PMC7835941/ /pubmed/33510768 http://dx.doi.org/10.3389/fgene.2020.572707 Text en Copyright © 2021 Wang, Wang, Piao, Li, Zhu, Li, Wang and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Wang, Weitie Wang, Yong Piao, Hulin Li, Bo Zhu, Zhicheng Li, Dan Wang, Tiance Liu, Kexiang Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells |
title | Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells |
title_full | Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells |
title_fullStr | Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells |
title_full_unstemmed | Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells |
title_short | Bioinformatics Analysis Reveals MicroRNA-193a-3p Regulates ACTG2 to Control Phenotype Switch in Human Vascular Smooth Muscle Cells |
title_sort | bioinformatics analysis reveals microrna-193a-3p regulates actg2 to control phenotype switch in human vascular smooth muscle cells |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835941/ https://www.ncbi.nlm.nih.gov/pubmed/33510768 http://dx.doi.org/10.3389/fgene.2020.572707 |
work_keys_str_mv | AT wangweitie bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT wangyong bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT piaohulin bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT libo bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT zhuzhicheng bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT lidan bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT wangtiance bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells AT liukexiang bioinformaticsanalysisrevealsmicrorna193a3pregulatesactg2tocontrolphenotypeswitchinhumanvascularsmoothmusclecells |