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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
Descripción
Sumario: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.