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Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction
Emerging evidence indicates that long non-coding RNAs (lncRNAs) serve as a critical molecular regulator in various cardiovascular diseases. Here, we aimed to identify and functionally characterize lncRNAs as potential mediators in the development of thoracic aortic dissection (TAD). We identified th...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685433/ https://www.ncbi.nlm.nih.gov/pubmed/34938738 http://dx.doi.org/10.3389/fcell.2021.792051 |
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author | Zhang, Song Zhao, Shiqi Han, Xuejie Zhang, Yun Jin, Xuexin Yuan, Yue Zhao, Xinbo Luo, Yingchun Zhou, Yun Gao, Yunlong Yu, Hui Sun, Danghui Xu, Wei Yan, Sen Gong, Yongtai Li, Yue |
author_facet | Zhang, Song Zhao, Shiqi Han, Xuejie Zhang, Yun Jin, Xuexin Yuan, Yue Zhao, Xinbo Luo, Yingchun Zhou, Yun Gao, Yunlong Yu, Hui Sun, Danghui Xu, Wei Yan, Sen Gong, Yongtai Li, Yue |
author_sort | Zhang, Song |
collection | PubMed |
description | Emerging evidence indicates that long non-coding RNAs (lncRNAs) serve as a critical molecular regulator in various cardiovascular diseases. Here, we aimed to identify and functionally characterize lncRNAs as potential mediators in the development of thoracic aortic dissection (TAD). We identified that a novel lncRNA, lnc-C2orf63-4-1, was lowly expressed in aortic samples of TAD patients and angiotensin II (Ang II)-challenged vascular smooth muscle cells (VSMCs), which was correlated with clinically aortic expansion. Besides, overexpression of lnc-C2orf63-4-1 significantly attenuated Ang II-induced apoptosis, phenotypic switching of VSMCs and degradation of extracellular matrix both in vitro and in vivo. A customized transcription factor array identified that signal transducer and activator of transcription 3 (STAT3) functioned as the main downstream effector. Mechanistically, dual-luciferase report analysis and RNA antisense purification (RAP) assay indicated that lnc-C2orf63-4-1 directly decreased the expression of STAT3, which was depend on the reduced stabilization of STAT3 mRNA. Importantly, up-regulation of STAT3 efficiently reversed the protective role of lnc-C2orf63-4-1 against Ang II-mediated vascular remodeling. Therefore, lnc-C2orf63-4-1 negatively regulated the expression of STAT3 and prevented the development of aortic dissection. Our study revealed that lnc-C2orf63-4-1 played a critical role in vascular homeostasis, and its dysfunction exacerbated Ang II-induced pathological vascular remodeling. |
format | Online Article Text |
id | pubmed-8685433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86854332021-12-21 Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction Zhang, Song Zhao, Shiqi Han, Xuejie Zhang, Yun Jin, Xuexin Yuan, Yue Zhao, Xinbo Luo, Yingchun Zhou, Yun Gao, Yunlong Yu, Hui Sun, Danghui Xu, Wei Yan, Sen Gong, Yongtai Li, Yue Front Cell Dev Biol Cell and Developmental Biology Emerging evidence indicates that long non-coding RNAs (lncRNAs) serve as a critical molecular regulator in various cardiovascular diseases. Here, we aimed to identify and functionally characterize lncRNAs as potential mediators in the development of thoracic aortic dissection (TAD). We identified that a novel lncRNA, lnc-C2orf63-4-1, was lowly expressed in aortic samples of TAD patients and angiotensin II (Ang II)-challenged vascular smooth muscle cells (VSMCs), which was correlated with clinically aortic expansion. Besides, overexpression of lnc-C2orf63-4-1 significantly attenuated Ang II-induced apoptosis, phenotypic switching of VSMCs and degradation of extracellular matrix both in vitro and in vivo. A customized transcription factor array identified that signal transducer and activator of transcription 3 (STAT3) functioned as the main downstream effector. Mechanistically, dual-luciferase report analysis and RNA antisense purification (RAP) assay indicated that lnc-C2orf63-4-1 directly decreased the expression of STAT3, which was depend on the reduced stabilization of STAT3 mRNA. Importantly, up-regulation of STAT3 efficiently reversed the protective role of lnc-C2orf63-4-1 against Ang II-mediated vascular remodeling. Therefore, lnc-C2orf63-4-1 negatively regulated the expression of STAT3 and prevented the development of aortic dissection. Our study revealed that lnc-C2orf63-4-1 played a critical role in vascular homeostasis, and its dysfunction exacerbated Ang II-induced pathological vascular remodeling. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8685433/ /pubmed/34938738 http://dx.doi.org/10.3389/fcell.2021.792051 Text en Copyright © 2021 Zhang, Zhao, Han, Zhang, Jin, Yuan, Zhao, Luo, Zhou, Gao, Yu, Sun, Xu, Yan, Gong and Li. https://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 | Cell and Developmental Biology Zhang, Song Zhao, Shiqi Han, Xuejie Zhang, Yun Jin, Xuexin Yuan, Yue Zhao, Xinbo Luo, Yingchun Zhou, Yun Gao, Yunlong Yu, Hui Sun, Danghui Xu, Wei Yan, Sen Gong, Yongtai Li, Yue Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction |
title | Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction |
title_full | Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction |
title_fullStr | Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction |
title_full_unstemmed | Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction |
title_short | Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction |
title_sort | lnc-c2orf63-4-1 confers vsmc homeostasis and prevents aortic dissection formation via stat3 interaction |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685433/ https://www.ncbi.nlm.nih.gov/pubmed/34938738 http://dx.doi.org/10.3389/fcell.2021.792051 |
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