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This study identified microRNAs involved in myocardial infarction (MI) through a novel system-level approach using RNA sequencing data in an MI mouse model. This approach involved the extraction of DEGs and DEmiRs from RNA-seq data in sham and MI samples and the subsequent selection of two miRNAs:  miR-30-5p  (family) and  miR-142a-5p , which were downregulated and upregulated in MI, respectively. Gene Set Enrichment Analysis (GSEA) using the predicted targets of the two miRNAs suggested that apoptosis is an essential gene ontology (GO)-associated term.  In vitro  functional assays using neonatal rat ventricular myocytes (NRVMs) demonstrated that  miR-30-5p  is anti-apoptotic and  miR-142a-5p  is pro-apoptotic. Luciferase assays showed that the apoptotic genes,  Picalm  and  Skil , and the anti-apoptotic genes,  Ghr  and  Kitl , are direct targets of  miR-30-5p  and  miR-142a-5p , respectively. siRNA studies verified the results of the luciferase assays for target validation. The results of the system-level high throughput approach identified a pair of functionally antagonistic miRNAs and their targets in MI. This study provides an in-depth analysis of the role of miRNAs in the pathogenesis of MI which could lead to the development of therapeutic tools. The system-level approach could be used to identify miRNAs involved in variety of other diseases.

A novel system-level approach using RNA-sequencing data identifies miR-30-5p and miR-142a-5p as key regulators of apoptosis in myocardial infarction