MicroRNA 199a-5p induces apoptosis by targeting JunB.

MicroRNA 199a-5p induces apoptosis by targeting JunB.
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MicroRNA 199a-5p 通过靶向 JunB 诱导细胞凋亡

DOI:
10.1038/s41598-018-24932-9
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发表时间:
2018-04-27
期刊:
影响因子:
4.6
通讯作者:
Yang P
Yang P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yan M;Yang S;Meng F;Zhao Z;Tian Z;Yang P

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MicroRNA参与包括心脏在内的各种器官中的各种生理和病理生理过程。我们之前的工作显示,miR-199 a-5 p在衰竭心脏中的水平显著高于对照心脏。然而,它是否与心力衰竭(HF)的进展和介导的心肌细胞凋亡仍不清楚。在本研究中,我们使用各种生物化学和分子生物学方法来研究急性心肌梗死诱导的大鼠模型中衰竭心脏中miR-199 a-5 p水平的变化。我们发现心脏中的miR-199 a-5 p水平随着HF的进展而增加,并且miR-199 a-5 p的过表达显著增加了未处理的H9 C2细胞的凋亡,并增强了血管紧张素II诱导的凋亡。因此,我们的研究结果表明,miR-199 a-5 p参与HF的进展,并介导心肌细胞凋亡。我们还通过双荧光素酶报告基因分析和对JunB基因3′端非翻译区的突变证实了激活蛋白1转录因子家族成员JunB是miR-199 a-5 p的直接靶点之一。与上述发现一致,在H9 c2细胞中过表达JunB抑制细胞凋亡。基于我们的发现,miR-199 a-5 p通过靶向JunB诱导细胞凋亡。
MicroRNAs participate in a variety of physiological and pathophysiological processes in various organs including the heart. Our previous work revealed that the level of miR-199a-5p was significantly higher in failing hearts than in control hearts. However, whether it is associated with the progression of heart failure (HF) and mediates cardiomyocyte apoptosis remained unclear. In the present study, we used various biochemical and molecular biological approaches to investigate the changes in miR-199a-5p levels in failing hearts in a rat model induced by acute myocardial infarction. We found that miR-199a-5p levels in the heart increased with the progression of HF, and overexpression of miR-199a-5p significantly increased apoptosis in untreated H9C2 cells and potentiated angiotensin II-induced apoptosis. Thus, our results indicate that miR-199a-5p is involved in the progression of HF and mediates cardiomyocyte apoptosis. We also confirmed that JunB, a member of the activator protein-1 transcription factor family, is one of direct targets of miR-199a-5p via a dual-luciferase reporter assay and mutagenesis on the 3′ untranslated region of the JunB gene. Consistent with the above findings, overexpression of JunB in H9c2 cells suppressed cell apoptosis. Based on our findings, miR-199a-5p induces apoptosis by targeting JunB.
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