Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction

• DOI: 10.3389/fcell.2021.792051
• Publication Date: 2021-12-06T06:41:53Z
• Authors: Song Zhang; Shiqi Zhao; Xuejie Han; Yun Zhang; Xuexin Jin; Yue Yuan; Xinbo Zhao; Yingchun Luo; Yun Zhou; Yunlong Gao; Hui Yu; Danghui Sun; Wei Xu; Sen Yan; Yongtai Gong; Yue Li
• Keywords: Homeostasis

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 potential mediators the development of thoracic aortic dissection (TAD). We identified novel lncRNA, lnc-C2orf63-4-1, was lowly expressed samples TAD patients angiotensin II (Ang II)-challenged vascular smooth muscle cells (VSMCs), which correlated with clinically expansion. Besides, overexpression lnc-C2orf63-4-1 significantly attenuated Ang II-induced apoptosis, phenotypic switching VSMCs degradation extracellular matrix both vitro vivo. A customized transcription factor array signal transducer activator 3 (STAT3) functioned main downstream effector. Mechanistically, dual-luciferase report analysis RNA antisense purification (RAP) assay indicated directly decreased expression STAT3, depend on reduced stabilization STAT3 mRNA. Importantly, up-regulation efficiently reversed protective role against II-mediated remodeling. Therefore, negatively regulated prevented dissection. Our study revealed played homeostasis, its dysfunction exacerbated pathological