敲低 circROBO2 通过调控 miR-1184/TRADD 轴减轻急性心肌梗死。
Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis.
机构信息
Department of Cardiology, the First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Longzi Lake District, Bengbu city, 233003, Anhui province, China.
出版信息
Mol Med. 2021 Mar 3;27(1):21. doi: 10.1186/s10020-021-00275-6.
BACKGROUND
Studies have found that circular RNAs (circRNAs) play key roles in cardiovascular diseases. However, the function of circROBO2 in acute myocardial infarction (AMI) is unclear. This study aimed to investigate the pathogenesis of circROBO2 in AMI.
METHODS
qRT-PCR and Western blot were used to determine the expression levels of circROBO2, miR-1184, and TRADD in AMI and sham-operated mouse models at mRNA and protein level, respectively. The relationship among miR-1184, circROBO2 and TRADD was evaluated by RNA immunoprecipitation (RIP) analysis and luciferase reporter gene analysis. The roles of circROBO2, miR-1184, and TRADD in myocardial cell apoptosis were evaluated using flow cytometry. Ultrasound echocardiography, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarction area, and myocardial cell apoptosis were measured to examine the effects of circROBO2 on myocardial injury.
RESULTS
The expression levels of miR-1184 were significantly reduced, and the expression levels of circROBO2 and TRADD were significantly increased in MI group. CircROBO2 acted as a sponge for miR-1184 by upregulating the expression of TRADD. In addition, overexpression of miR-1184 enhanced the protective effect of knockdown of circROBO2 by partially inhibiting the expression of TRADD in vivo and in vitro.
CONCLUSION
Knockdown of circROBO2 reduced the apoptosis of cardiomyocytes by increasing the expression levels of miR-1184, which in turn decreased the expression levels of TRADD in the myocardium post-MI.
背景
研究发现环状 RNA（circRNAs）在心血管疾病中发挥关键作用。然而，circROBO2 在急性心肌梗死（AMI）中的功能尚不清楚。本研究旨在探讨 circROBO2 在 AMI 中的发病机制。
方法
qRT-PCR 和 Western blot 分别用于检测 AMI 和假手术小鼠模型中 circROBO2、miR-1184 和 TRADD 的 mRNA 和蛋白水平表达。通过 RNA 免疫沉淀（RIP）分析和荧光素酶报告基因分析评估 miR-1184、circROBO2 和 TRADD 之间的关系。通过流式细胞术评估 circROBO2、miR-1184 和 TRADD 在心肌细胞凋亡中的作用。超声心动图、血清肌酸激酶 MB（CK-MB）和乳酸脱氢酶（LDH）、心肌梗死面积和心肌细胞凋亡用于检测 circROBO2 对心肌损伤的影响。
结果
miR-1184 的表达水平明显降低，而 circROBO2 和 TRADD 的表达水平明显升高。circROBO2 通过上调 TRADD 的表达充当 miR-1184 的海绵。此外，miR-1184 的过表达通过部分抑制体内和体外 circROBO2 敲低时 TRADD 的表达，增强了对 circROBO2 敲低的保护作用。
结论
circROBO2 的敲低通过增加 miR-1184 的表达水平减少心肌细胞的凋亡，从而降低心肌梗死后心肌中 TRADD 的表达水平。
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