Department of Neurosurgery, The Second Clinical Medical School of Inner Mongolia University for Nationalities, Yakeshi, Inner Mongolia, 022150, China.
Department of Neurosurgery, Sanbo Brain Hospital Co., Ltd, Beijing, 100093, China.
Biosci Rep. 2021 Mar 26;41(3). 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.
长链非编码 RNA（lncRNA）已被确定为腹主动脉瘤（AAA）发展的重要调节因子。在这项研究中，评估了 lncRNA X 失活特异性转录物（XIST）在血管平滑肌细胞（VSMCs）演化中的功能和分子机制。结果表明，AAA 患者血清中 XIST 的表达增加，但 miR-1264 的表达水平降低。XIST 耗竭会阻碍人主动脉平滑肌细胞（HA-VSMCs）的增殖能力并刺激细胞凋亡，而通过直接相互作用抑制 miR-1264 的表达。此外，miR-1264 抑制剂可挽救 XIST 敲低对细胞凋亡和增殖的影响。随后的分子研究表明，WNT5A 是 miR-1264 的靶标，而 XIST 作为 miR-1264 的竞争性内源性 RNA（ceRNA），可提高 WNT5A 的表达。此外，miR-1264 抑制剂通过激活 WNT/β-catenin 信号通路，刺激 HA-VSMCs 的增殖并抑制其凋亡。综上所述，XIST 通过 miR-1264 抑制 HA-VSMCs 的凋亡并刺激其增殖，从而在 AAA 中发挥作用。
