miR‑217 and miR‑543 downregulation mitigates inflammatory response and myocardial injury in children with viral myocarditis by regulating the SIRT1/AMPK/NF‑κB signaling pathway.

Abstract

The aim of the present study was to investigate the expression levels and roles of microRNA (miR)‑217 and miR‑543 in viral myocarditis, and to examine their underlying mechanisms. Coxsackievirus B3 (CVB3) was used to establish in\xa0vivo and in\xa0vitro models of viral myocarditis. The levels of miR‑217 and miR‑543 were detected using reverse transcription‑quantitative PCR. The association between miR‑217 and miR‑543 and sirtuin‑1 (SIRT1) was predicted and confirmed by TargetScan and dual‑luciferase reporter assay. Cell viability was detected using Cell Counting Kit‑8 assay, and cell apoptosis was measured by analyzing the expression levels of Bcl‑2 and Bax, and by flow cytometry. In addition, the synthesis of various pro‑inflammatory factors was determined by ELISA. In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were measured in cardiomyocytes following transfection and CVB infection. miR‑217 and miR‑543 were found to be highly expressed in the peripheral blood of pediatric patients with viral myocarditis, in the peripheral blood and myocardial tissues of viral myocarditis mice and in CVB3‑infected cardiomyocytes. SIRT1 was found to be a target of both miR‑217 and miR‑543, and SIRT1 expression level was downregulated in viral myocarditis. Further analysis indicated that the reduced cell viability, increased cell apoptosis, enhanced synthesis of inflammatory factors, increased MDA content and decreased SOD activity associated with myocarditis were significantly reversed after inhibition of miR‑217 or miR‑543. Importantly, the present results showed that all the effects of miR‑217 and miR‑543 inhibition on cardiomyocytes were significantly suppressed following SIRT1 knockdown. Collectively, the present data indicated that miR‑217 and miR‑543 were significantly upregulated in viral myocarditis, and downregulation of miR‑217 and miR‑543 attenuated CVB3 infection‑induced cardiomyocyte injury by targeting SIRT1. miR‑217 and miR‑543 may be potential therapeutic targets for developing novel viral myocarditis treatments in the future.