Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis

Tian-Ping Chen,Si-Gan Hu,Hong-Ju Wang,Nai-Ju Zhang,Xu Geng

doi:10.1186/s10020-021-00275-6

Tian-Ping Chen, Si-Gan Hu + Show 3 more

Open Access

https://doi.org/10.1186/s10020-021-00275-6

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Abstract

BackgroundStudies 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.MethodsqRT-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.ResultsThe 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.ConclusionKnockdown 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.

Highlights

Acute myocardial infarction (AMI) is a major cause of ischemic cardiomyopathy (Worner et al 2013)
Consistent with our results in ischemic myocardium, the expression levels of circROBO2 were gradually increased in a time-dependent manner in primary myocardial cells exposed to ischemic injury (P < 0.05)
The results indicated that circROBO2 was induced in the infarct region compared to the adjacent normal tissues, but was slightly induced in the remote region

Summary

Introduction

Acute myocardial infarction (AMI) is a major cause of ischemic cardiomyopathy (Worner et al 2013). With the development of RNA sequencing technologies and biophysical technology, extensive studies have investigated the roles of circRNAs in gene regulation and disease occurrence (Yang et al 2019; Wang et al 2019). Recent studies have shown that some circRNAs are involved in the development of various cardiovascular diseases, including myocardial infarction, cardiac metabolic disease and heart failure (Jiang et al 2016; Fan et al 2017). The potential roles that circRNAs play in cardiovascular disease have been identified (Corsten et al 2010). CircROBO2 is a newly identified circRNA and its role in AMI remains unclear. Studies have found that circular RNAs (circRNAs) play key roles in cardiovascular diseases. The function of circROBO2 in acute myocardial infarction (AMI) is unclear. This study aimed to investigate the pathogen‐ esis of circROBO2 in AMI

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