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miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2

MicroRNAs (miRNAs) dysregulation is tightly related to diseases including tumor, neuro disease and cardiovascular disease. In this study, we investigated the potential biological effects of miR-34a and its target CXCR3 in phenotypic modulation of vascular smooth muscle cells (VSMCs) of intracranial...

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Autores principales: Yuan, Xuesong, Bian, Xiaoxing, Wei, Wenfeng, Bao, Qing, Liu, Ping, Jiang, Wenqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Genética 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075123/
https://www.ncbi.nlm.nih.gov/pubmed/33901269
http://dx.doi.org/10.1590/1678-4685-GMB-2020-0124
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author Yuan, Xuesong
Bian, Xiaoxing
Wei, Wenfeng
Bao, Qing
Liu, Ping
Jiang, Wenqing
author_facet Yuan, Xuesong
Bian, Xiaoxing
Wei, Wenfeng
Bao, Qing
Liu, Ping
Jiang, Wenqing
author_sort Yuan, Xuesong
collection PubMed
description MicroRNAs (miRNAs) dysregulation is tightly related to diseases including tumor, neuro disease and cardiovascular disease. In this study, we investigated the potential biological effects of miR-34a and its target CXCR3 in phenotypic modulation of vascular smooth muscle cells (VSMCs) of intracranial aneurysms (IAs). MiR-34a was found to be down-regulated in IAs patients tested by Real-time PCR and decreased in GEO data. Meanwhile, our study also showed miR-34a inhibited matrix metalloproteinases (MMPs) and migration of VSMCs. Besides, CXCR3 is a direct target of miR-34a identified via luciferase assay. CXCR3 showed inhibitory effect on SM-MHC, SM22 while promoted MMPs expression, cell proliferation and migration in VSMCs. MiR-34a reversed the effect of CXCR3 in VSMCs. In addition, MMP-2 is a competitive endogenous RNA (ceRNA) of CXCR3 sharing common miR-34a target. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sponging endogenous miR-34a. In conclusion, miR-34a is down-regulated in IAs while CXCR3 is the direct target of miR-34a that regulates phenotypic modulation of VSMCs. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sharing common miR-34a targets.
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spelling pubmed-80751232021-05-06 miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2 Yuan, Xuesong Bian, Xiaoxing Wei, Wenfeng Bao, Qing Liu, Ping Jiang, Wenqing Genet Mol Biol Human and Medical Genetics MicroRNAs (miRNAs) dysregulation is tightly related to diseases including tumor, neuro disease and cardiovascular disease. In this study, we investigated the potential biological effects of miR-34a and its target CXCR3 in phenotypic modulation of vascular smooth muscle cells (VSMCs) of intracranial aneurysms (IAs). MiR-34a was found to be down-regulated in IAs patients tested by Real-time PCR and decreased in GEO data. Meanwhile, our study also showed miR-34a inhibited matrix metalloproteinases (MMPs) and migration of VSMCs. Besides, CXCR3 is a direct target of miR-34a identified via luciferase assay. CXCR3 showed inhibitory effect on SM-MHC, SM22 while promoted MMPs expression, cell proliferation and migration in VSMCs. MiR-34a reversed the effect of CXCR3 in VSMCs. In addition, MMP-2 is a competitive endogenous RNA (ceRNA) of CXCR3 sharing common miR-34a target. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sponging endogenous miR-34a. In conclusion, miR-34a is down-regulated in IAs while CXCR3 is the direct target of miR-34a that regulates phenotypic modulation of VSMCs. CXCR3 increased MMP-2 level through competitive endogenous RNA regulation by sharing common miR-34a targets. Sociedade Brasileira de Genética 2021-04-23 /pmc/articles/PMC8075123/ /pubmed/33901269 http://dx.doi.org/10.1590/1678-4685-GMB-2020-0124 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License
spellingShingle Human and Medical Genetics
Yuan, Xuesong
Bian, Xiaoxing
Wei, Wenfeng
Bao, Qing
Liu, Ping
Jiang, Wenqing
miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2
title miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2
title_full miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2
title_fullStr miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2
title_full_unstemmed miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2
title_short miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2
title_sort mir-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting cxcr3 and mmp-2
topic Human and Medical Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075123/
https://www.ncbi.nlm.nih.gov/pubmed/33901269
http://dx.doi.org/10.1590/1678-4685-GMB-2020-0124
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