Altered exosomal miR-181d and miR-30a related to the pathogenesis of CVB3 induced myocarditis by targeting SOCS3.

ABSTRACT

OBJECTIVE: MicroRNAs are a group of gene expression regulators and some of which have been confirmed to be associated with acute viral myocarditis (VM). This study aims to find new biomarkers for VM diagnosis and explore the roles of miRNAs during the pathogenesis of VM. PATIENTS AND METHODS: 23 patients with acute myocarditis and 12 controls were included in this research. The expression of 10 candidate miRNAs in the serum exosome was examined by qRT-PCR. The direct targets were predicted using bioinformatics tools and then confirmed by dual luciferase assay and immunoblotting. Levels IL-6 of cell culture supernatants were determined by enzyme-linked immunosorbent assay. Six weeks old male mice were injected intraperitoneally with Coxsackievirus B3 (CVB3) and then treated by miRNA inhibitors through tail vein injection. RESULTS: Five miRNAs were found to have disturbed expression in the exosome and may have the potential to be used as biomarker for VM diagnosis. Meanwhile, the expression of miR-30a and -181d was also altered in the cells after CVB3 infection. We identified SOCS3 as a direct target of miR-30a and -181d. Furthermore, during CVB3 infection, up-regulated miR-30a and -181d are related to enhanced IL-6 level via modulating SOCS3 expression. miRNA inhibitors injection increased mice survival rate after CVB3 infection. CONCLUSIONS: miR-30a and -181d contribute to the over-activated inflammatory response to viral infection of the heart during coxsackievirus infection.