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长链非编码 RNA Sox2ot 沉默通过 microRNA-145 介导的 Egr1 抑制抑制腹主动脉瘤血管平滑肌细胞的氧化应激和炎症。

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.

机构信息

Department of Cardiovascular Surgery, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, P.R. China.

Department of Cardiology, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, P.R. China.

出版信息

Aging (Albany NY). 2020 Jul 6;12(13):12684-12702. doi: 10.18632/aging.103077.

DOI:10.18632/aging.103077
PMID:32629426
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377859/
Abstract

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 and , 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.

摘要

长链非编码 RNA(lncRNA)在腹主动脉瘤(AAA)的发生和发展中起重要作用,AAA 是一种常见的血管退行性疾病。本研究旨在探讨 lncRNA Sox2ot 在 AAA 发生发展中的可能作用。本研究发现,lncRNA Sox2ot 和早期生长反应因子 1(Egr1)在 Ang II 诱导的 AAA 小鼠和氧化应激诱导的血管平滑肌细胞(VSMC)模型中高表达,而 microRNA(miR)-145 低表达。Egr1 是 miR-145 的潜在靶基因,lncRNA Sox2ot 可以竞争性结合 miR-145 来上调 Egr1 的表达。过表达 miR-145-5p 被发现通过抑制 Egr1 来抑制氧化应激和炎症,而 lncRNA Sox2ot 则拮抗了这一作用。综上所述,本研究提供的证据表明,下调 lncRNA Sox2ot 通过调节 miR-145 抑制 Egr1 的表达,从而抑制 AAA 的发展,为 AAA 的治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/7377859/c057f7b7fdf4/aging-12-103077-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/7377859/71f06a3a4e84/aging-12-103077-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204e/7377859/c057f7b7fdf4/aging-12-103077-g008.jpg
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