Department of Internal Medicine and Cardiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China.
Sci Rep. 2018 Apr 27;8(1):6699. doi: 10.1038/s41598-018-24932-9.
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.
微小 RNA 参与包括心脏在内的各种器官中的多种生理和病理生理过程。我们之前的工作表明，miR-199a-5p 的水平在衰竭的心脏中明显高于对照心脏。然而，它是否与心力衰竭（HF）的进展有关，并介导心肌细胞凋亡尚不清楚。在本研究中，我们使用各种生化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-199a-5p 水平的变化。我们发现，随着 HF 的进展，心脏中 miR-199a-5p 的水平增加，miR-199a-5p 的过表达显著增加未处理的 H9C2 细胞中的凋亡，并增强血管紧张素 II 诱导的凋亡。因此，我们的结果表明，miR-199a-5p 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检测和 JunB 基因 3'非翻译区的突变证实，JunB，激活蛋白-1 转录因子家族的成员之一，是 miR-199a-5p 的直接靶标之一。与上述发现一致，在 H9c2 细胞中过表达 JunB 可抑制细胞凋亡。基于我们的发现，miR-199a-5p 通过靶向 JunB 诱导细胞凋亡。
