Silencing of long non-coding RNA Sox2ot inhibits oxidative stress and inflammation of vascular smooth muscle cells in abdominal aortic aneurysm via microRNA-145-mediated Egr1 inhibition
Silencing of long non-coding RNA Sox2ot inhibits oxidative stress and inflammation of vascular smooth muscle cells in abdominal aortic aneurysm via microRNA-145-mediated Egr1 inhibition
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沉默长链非编码RNA Sox 2 ot通过microRNA-145介导的Egr 1抑制腹主动脉瘤血管平滑肌细胞的氧化应激和炎症
DOI：
10.18632/aging.103077
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发表时间：
2020-07-15
期刊：
影响因子：
5.2
通讯作者：
Wang, Ren
中科院分区：
文献类型：
--
作者：
Lin, Huyu;You, Bin;Wang, Ren
长链非编码RNA（lncRNA）已被大量报道参与腹主动脉瘤（AAA）的发生和发展，腹主动脉瘤是一种常见的血管退行性疾病。本研究旨在探讨lncRNA Sox 2 ot在AAA发生发展中的可能作用。在本研究中，我们发现lncRNA Sox 2 ot和早期生长反应因子-1（Egr 1）在Ang II诱导的AAA小鼠和氧化应激诱发的血管平滑肌细胞（VSMC）模型中高表达，而microRNA（miR）-145低表达。Egr 1是miR-145的潜在靶基因，lncRNA Sox 2 ot可竞争性结合miR-145上调Egr 1的表达。发现miR-145- 5 p的过表达通过在体内和体外抑制Egr 1来减轻氧化应激和炎症，这被lncRNA Sox 2 ot抵消。综上所述，本研究提供的证据表明，下调lncRNA Sox 2 ot通过调节miR-145抑制Egr 1的表达，从而抑制AAA的发展，突出了AAA治疗的理论基础。
Long non-coding RNAs (lncRNAs) have been largely reported to contribute to the development and progression of abdominal aortic aneurysm (AAA), a common vascular degenerative disease. The present study was set out with the aim to investigate the possible role of lncRNA Sox2ot in the development of AAA. In this study, we found that lncRNA Sox2ot and early growth response factor-1 (Egr1) were highly expressed, while microRNA (miR)-145 was poorly expressed in Ang II -induced AAA mice and oxidative stress-provoked vascular smooth muscle cell (VSMC) model. Egr1 was a potential target gene of miR-145, and lncRNA Sox2ot could competitively bind to miR-145 to upregulate Egr1 expression. Overexpression of miR-145-5p was found to attenuate oxidative stress and inflammation by inhibiting Egr1 both in vivo and in vitro , which was counteracted by lncRNA Sox2ot. Taken together, the present study provides evidence that downregulation of lncRNA Sox2ot suppressed the expression of Egr1 through regulating miR-145, thus inhibiting the development of AAA, highlighting a theoretical basis for AAA treatment.