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MicroRNA-98 通过抑制 DAPK1 的表达来减轻心脏缺血再灌注损伤。

MicroRNA-98 attenuates cardiac ischemia-reperfusion injury through inhibiting DAPK1 expression.

机构信息

Department of Cardiovascular Diseases, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China.

Department of Cardiovascular Diseases, The Frist Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China.

出版信息

IUBMB Life. 2019 Feb;71(2):166-176. doi: 10.1002/iub.1879. Epub 2018 Nov 12.

Abstract

Cardiovascular ischemic disease is a large class of diseases that are harmful to human health. The significant role of microRNAs (miRNAs) in terms of controlling cardiac injury has been reported in latest studies. MiR-98 is very important in regulating the apoptosis, the differentiation, the growth as well as the metastasis of cells. Nevertheless, the effect of miR-98 in the cardiac ischemia reperfusion (I/R) injury has rarely been investigated. In the current research, we found that the miR-98 expression was down-regulated in the cardiomyocytes subjected to hypoxia/reoxygenation (H/R) and in the myocardium of the I/R rats. In addition, over-expression of miR-98 could significantly reduce the myocardial oxidative stress and ischemic injury as well as cell apoptosis. In agreement, similar findings were demonstrated in H9c2 cells subjected to H/R injury. Bioinformatic analysis using MiRanda and TargetScan and luciferase activity assay confirmed death-associated protein kinase 1 (DAPK1) as a direct target of miR-98. These findings suggest that miR-98 may be exploited as a novel molecular marker or therapeutic target for myocardial I/R injury. © 2018 IUBMB Life, 71(1):166-176, 2019.

摘要

心血管缺血性疾病是一大类危害人类健康的疾病。最近的研究报道,微小 RNA(miRNA)在控制心脏损伤方面具有重要作用。miR-98 在调节细胞凋亡、分化、生长和转移方面非常重要。然而,miR-98 在心肌缺血再灌注(I/R)损伤中的作用很少被研究。在本研究中,我们发现缺氧/复氧(H/R)处理的心肌细胞和 I/R 大鼠心肌中 miR-98 的表达下调。此外,过表达 miR-98 可显著减轻心肌氧化应激和缺血性损伤以及细胞凋亡。在 H9c2 细胞的 H/R 损伤模型中也得到了类似的发现。利用 MiRanda 和 TargetScan 的生物信息学分析和荧光素酶活性测定证实了凋亡相关蛋白激酶 1(DAPK1)是 miR-98 的直接靶标。这些发现表明,miR-98 可作为心肌 I/R 损伤的新型分子标志物或治疗靶点。

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