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XIST knockdown suppresses vascular smooth muscle cell proliferation and induces apoptosis by regulating miR-1264/WNT5A/β-catenin signaling in aneurysm.
Bioscience Reports ( IF 3.8 ) Pub Date : 2021-01-27 , DOI: 10.1042/bsr20201810
Liang Zou 1 , Peng-Fei Xia 1 , Lei Chen 2 , Yan-Yan Hou 3
Affiliation  

LncRNAs have been ascertained as vital modulators in abdominal aortic aneurysm (AAA) development. In this research, the function and molecular mechanisms of the lncRNA 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 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 a miR-1264 inhibitor. Subsequent molecular investigations indicated that WNT5A was miR-1264's target, and XIST functioned as a ceRNA of miR-1264 to raise WNT5A expression. Further, a 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.

中文翻译:

XIST 敲低通过调节动脉瘤中的 miR-1264/WNT5A/β-catenin 信号传导来抑制血管平滑肌细胞增殖并诱导细胞凋亡。

LncRNA 已被确定为腹主动脉瘤 (AAA) 发展中的重要调节剂。本研究评估了 lncRNA XIST 在血管平滑肌细胞 (VSMCs) 进化中的功能和分子机制。结果显示,AAA 患者血清中 XIST 表达增加,但 miR-1264 表达水平降低。XIST 耗竭阻碍了 HA-VSMCs 增殖和刺激细胞凋亡的能力,同时通过非介导的相互作用抑制了 miR-1264 的表达。此外,XIST 敲低对细胞凋亡和增殖的影响可以通过 miR-1264 抑制剂来挽救。随后的分子研究表明,WNT5A 是 miR-1264 的靶标,XIST 作为 miR-1264 的 ceRNA 发挥作用以提高 WNT5A 的表达。进一步,一种 miR-1264 抑制剂通过激活 WNT/β-catenin 信号传导刺激 HA-VSMCs 的增殖并抑制其凋亡。总之,XIST 通过 miR-1264 的 WNT/β-catenin 信号通路阻碍细胞凋亡并刺激 HA-VSMC 的增殖,证明了 XIST 在 AAA 中的潜在作用。
更新日期:2021-01-29
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