MicroRNA-381 protects myocardial cell function in children and mice with viral myocarditis via targeting cyclooxygenase-2 expression

MicroRNA-381 通过靶向环氧合酶-2 表达保护病毒性心肌炎儿童和小鼠的心肌细胞功能

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作者:Yong Zhang, Lingli Sun, Hui Sun, Zhongqin Yu, Xia Liu, Xia Luo, Cuifang Li, Dongming Sun, Tao Li

Abstract

The present study aimed to determine the expression of cyclooxygenase (COX)-2 and microRNA (miRNA/miR)-381 in the blood of children with viral myocarditis (VM), and investigate the association between COX-2 and miR-381 in the occurrence and development of the disease using a mouse model. A total of 26 children with VM (15 boys and 11 girls) were included in the present study. Peripheral blood was collected from all children. The mouse model of VM was constructed by coxsackievirus B3 (CVB3) infection. Peripheral blood and myocardial tissues were collected from all mice for analysis. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of COX-2 mRNA and miR-381 in serum and myocardial tissues. ELISA was used to measure the content of COX-2 protein in serum from humans and mice, and western blotting was employed to determine the expression of COX-2 protein in myocardial tissues from mice. Contents of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) were evaluated using an automatic biochemical analyzer. A dual luciferase assay was conducted to identify interactions between COX-2 mRNA and miR-381. Children with VM had increased COX-2 levels and decreased miR-381 expression in peripheral blood, compared with those who had recovered from VM. CVB3 infection resulted in damage in the myocardium of mice, and elevated CK-MB and LDH contents. VM model mice exhibited increased COX-2 levels and decreased miR-381 expression in peripheral blood and myocardial tissues compared with normal mice. miR-381 binds to the 3'-untranslated seed regions of both human and mouse COX-2 mRNA to regulate their expression. The present study demonstrated that children with VM have decreased miR-381 expression and elevated COX-2 expression in peripheral blood. miR-381 may inhibit myocardial cell damage caused by CVB3 infection and protect myocardial cell function by targeting COX-2 expression.

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