XIST knockdown suppresses vascular smooth muscle cell proliferation and induces apoptosis by regulating miR-1264/WNT5A/β-catenin signaling in aneurysm

• Published in: Bioscience reports Vol. 41; no. 3
• Main Authors: Zou, Liang, Xia, Peng-Fei, Chen, Lei, Hou, Yan-Yan
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 26.03.2021; Portland Press Ltd
• Subjects: Aged; Aneurysms; Animals; Aorta; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - metabolism; Aortic aneurysms; Apoptosis; beta Catenin - metabolism; Binding sites; Cancer; Cell growth; Cell Proliferation; Cells, Cultured; Coronary vessels; Disease; Epigenetics; Female; Humans; Inhibitors; Laboratory animals; Male; Medical diagnosis; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - metabolism; Middle Aged; Modulators; Molecular modelling; Muscle, Smooth, Vascular - cytology; Muscles; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - physiology; Non-coding RNA; Plasmids; Proteins; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal transduction; Smooth muscle; Wnt protein; Wnt Signaling Pathway; Wnt-5a Protein - metabolism; β-Catenin; Mongolia; China; miR-1264; lncRNA; proliferation; abdominal aortic aneurysm
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20201810

Long non-coding RNAs (lncRNAs) have been ascertained as vital modulators in abdominal aortic aneurysm (AAA) development. In this research, the function and molecular mechanisms of the lncRNA X-inactive specific transcript (XIST) in the evolution of vascular smooth muscle cells (VSMCs) were assessed. Results showed that XIST expression was increased but miR-1264 expression level was reduced in the serum of AAA patients. XIST depletion impeded human aorta VSMCs (HA-VSMCs') ability to proliferate and stimulate apoptosis, while repressing miR-1264 expression through an unmediated interaction. Additionally, the influence of XIST knockdown on apoptosis and proliferation could be rescued by an miR-1264 inhibitor. Subsequent molecular investigations indicated that WNT5A was miR-1264's target, and XIST functioned as a competing endogenous RNA (ceRNA) of miR-1264 to raise WNT5A expression. Further, an miR-1264 inhibitor stimulated the proliferation and suppressed the apoptosis of HA-VSMCs through the activation of WNT/β-catenin signaling. Taken together, XIST impeded the apoptosis and stimulated the proliferation of HA-VSMCs via the WNT/β-catenin signaling pathway through miR-1264, demonstrating XIST's underlying role in AAA.