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hsa-let-7g miRNA 靶向 caspase-3 并抑制 ox-LDL 诱导的内皮细胞凋亡。

Hsa-let-7g miRNA targets caspase-3 and inhibits the apoptosis induced by ox-LDL in endothelial cells.

机构信息

Emergency Department, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

出版信息

Int J Mol Sci. 2013 Nov 18;14(11):22708-20. doi: 10.3390/ijms141122708.

Abstract

It has been well confirmed ox-LDL plays key roles in the development of atherosclerosis via binding to LOX-1 and inducing apoptosis in vascular endothelial cells. Recent studies have shown ox-LDL can suppress microRNA has-let-7g, which in turn inhibits the ox-LDL induced apoptosis. However, details need to be uncovered. To determine the anti-atherosclerosis effect of microRNA has-let-7g, and to evaluate the possibility of CASP3 as an anti-atherosclerotic drug target by has-let-7g, the present study determined the role of hsa-let-7g miRNA in ox-LDL induced apoptosis in the vascular endothelial cells. We found that miRNA has-let-7g was suppressed during the ox-LDL-induced apoptosis in EAhy926 endothelial cells. In addition, overexpression of has-let-7g negatively regulated apoptosis in the endothelial cells by targeting caspase-3 expression. Therefore, miRNA let-7g may play important role in endothelial apoptosis and atherosclerosis.

摘要

已经充分证实,氧化型低密度脂蛋白(ox-LDL)通过与清道夫受体 LOX-1 结合并诱导血管内皮细胞凋亡,在动脉粥样硬化的发生发展中发挥关键作用。最近的研究表明,ox-LDL 可以抑制 microRNA has-let-7g,进而抑制 ox-LDL 诱导的细胞凋亡。然而,其中的细节仍有待揭示。为了确定 microRNA has-let-7g 的抗动脉粥样硬化作用,并评估 CASP3 作为 microRNA has-let-7g 的抗动脉粥样硬化药物靶点的可能性,本研究旨在确定 has-let-7g miRNA 在 ox-LDL 诱导的血管内皮细胞凋亡中的作用。我们发现,在 EAhy926 内皮细胞中,ox-LDL 诱导的细胞凋亡过程中 microRNA has-let-7g 受到抑制。此外,过表达 has-let-7g 通过靶向 caspase-3 表达负调控内皮细胞凋亡。因此,miRNA let-7g 可能在血管内皮细胞凋亡和动脉粥样硬化中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8634/3856086/b20bd879dcd2/ijms-14-22708f1.jpg

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