{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:52:55Z","timestamp":1787644375343,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>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 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. 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.<\/jats:p>","DOI":"10.3389\/fcell.2021.792051","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T06:41:53Z","timestamp":1638772913000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Lnc-C2orf63-4-1 Confers VSMC Homeostasis and Prevents Aortic Dissection Formation via STAT3 Interaction"],"prefix":"10.3389","volume":"9","author":[{"given":"Song","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danghui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtai","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1016\/j.jtcvs.2009.07.075","article-title":"Smooth Muscle Phenotypic Modulation Is an Early Event in Aortic Aneurysms","volume":"138","author":"Ailawadi","year":"2009","journal-title":"J. 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