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微小RNA-199a通过靶向作用作为心肌细胞自噬的潜在抑制因子。

MicroRNA-199a acts as a potential suppressor of cardiomyocyte autophagy through targeting .

作者信息

Chen Liang, Wang Fei-Yu, Zeng Zhen-Yu, Cui Ling, Shen Jian, Song Xiao-Wei, Li Pan, Zhao Xian-Xian, Qin Yong-Wen

机构信息

Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

出版信息

Oncotarget. 2017 Jul 10;8(38):63825-63834. doi: 10.18632/oncotarget.19133. eCollection 2017 Sep 8.

Abstract

Autophagy is an adaptive response to cardiomyocytes survival under stress conditions. MicroRNAs (miRNAs, miR) have been described to act as potent modulators of autophagy. To investigate whether and how miR-199a modulated autophagy , primary cardiomyocytes were treated under starvation to induce autophagy. Results showed that down-regulation of miR-199a was sufficient to activate cardiomyocytes autophagy. MiR-199a suppressed cardiomyocytes autophagy through direct inhibiting heat shock protein family A member 5 (). Forced overexpression of recovered the inhibitory effect of miR-199a in autophagy activation. Our results suggested miR-199a as an effective suppressor of starvation-induced cardiomyocytes autophagy and that was a direct target during this process. These results extend the understanding of the role and pathway of miR-199a in cardiomyocytes autophagy, and may introduce a potential therapeutic strategy for the protection of cardiomyocytes in myocardial infarction or ischemic heart disease.

摘要

自噬是应激条件下心肌细胞生存的一种适应性反应。微小RNA(miRNA,miR)已被描述为自噬的有效调节因子。为了研究miR-199a是否以及如何调节自噬,原代心肌细胞在饥饿条件下进行处理以诱导自噬。结果表明,miR-199a的下调足以激活心肌细胞自噬。miR-199a通过直接抑制热休克蛋白家族A成员5来抑制心肌细胞自噬。热休克蛋白家族A成员5的强制过表达恢复了miR-199a对自噬激活的抑制作用。我们的结果表明miR-199a是饥饿诱导的心肌细胞自噬的有效抑制因子,并且热休克蛋白家族A成员5在此过程中是直接靶点。这些结果扩展了对miR-199a在心肌细胞自噬中的作用和途径的理解,并可能为心肌梗死或缺血性心脏病中保护心肌细胞引入一种潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91db/5609964/046509846f4c/oncotarget-08-63825-g001.jpg

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