Upregulated microRNA-214 enhances cardiac injury by targeting ITCH during coxsackievirus infection.

Viral myocarditis (VM), a severe clinical condition characterized by cardiac inflammation, is most frequently induced as a result of coxsackievirus infection. Evidence suggests that microRNAs may have significant roles in the progression of cardiac injury during coxsackievirus infection. Concurrently, microRNA (miR)-214 was found to be upregulated in the plasma and myocardial cells during this process. In the present study, eight candidate miRNAs, the functions of which are associated with myocarditis, were selected and their expression levels were evaluated by reverse transcription-quantitative polymerase chain reaction. miR-146b and miR-214 were found to have significantly upregulated expression levels in the heart tissues of patients with VM compared with those of the control subjects. Predictions via the use of online bioin-formatics tools and confirmed by dual-luciferase assay and western blot analysis, revealed that ITCH, an NF-B signaling suppressor, was a target gene of miR-214. To investigate the biological function of miR-214, tumor necrosis factor- and interleukin-6 expression levels were evaluated in HeLa cell culture supernatant. The results revealed that miR-214 over-expression enhanced the expression of the two cytokines. In addition, the function of miR-214 was partially rescued by ITCH overexpression. Subsequently, concurrent results were obtained following experiments in murine cardiac myocytes. In conclusion, the results of the present study demonstrated that miR-214 contributed to the adverse inflammatory response to viral infection of the heart during coxsackievirus infection and is therefore a potential therapeutic target for the treatment of viral myocarditis.