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

Abstract

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. IntroductionThe incidence of viral myocarditis (VM) is gradually increased in recent years, and attracts the attention of more and more scholars (1). Coxsackievirus B3 (CVB3) is one of the most common viruses that cause VM (2). VM can develop into acute heart failure (3,4). According to available clinical studies, the mortality rate of VM in young people is as high as 21%, and sudden deaths caused by VM or fatal ventricular arrhythmias in children account for about 20% (5,6). However, there have been few effective therapies for VM by now. Current treatment for VM is still focused on the control of cardiac arrhythmia and heart failure. Therefore, it is necessary to study the molecular mechanism of VM.VM is a common infectious disease in pediatric clinical practice. It is caused by viral infection or disturbance of autoimmune system, and characterized by localized or diffuse acute or chronic inflammatory lesions of the myocardium (1,7). In inflammation, cyclooxygenase (COX), especially COX-2 in the COX family, plays an important role. COX-2 is produced after induction by external stimuli (physical...

Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

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MicroRNAs in Inflammatory Heart Diseases and Sepsis-Induced Cardiac Dysfunction: A Potential Scope for the Future?

“…Further experiments elucidated the role of miR-141-3p, which seems to suppress STAT4, a central component of the JAK/STAT pathway, which plays an important role in inflammatory processes [36]. Similarly, miR-318 is downregulated in patients with myocarditis, which results in an overexpression of cyclooxygenase 2 (COX2) that promotes inflammation [37]. In contrast, miR-30a and miR-181d were found to promote myocardial inflammation by targeting suppressor of cytokine signaling 3 (SOCS3), and an inhibition of these miRNAs significantly decreases mortality in a murine model of CVB3-induced viral myocarditis [38].…”

The Role of Non-coding RNAs in Viral Myocarditis

“…On the contrary, miR-381, miR-133b, and miR-27b act as anti-inflammatory factors. MiR-381 relieved myocardial injury by targeting cytochrome c oxidase subunit II (COX-2) (Zhang Y. et al, 2018 ), miR-133b reduced IL-6 and TNF-α by directly targeting RAB27B, member RAS oncogene family (Rab27B) (Zhang et al, 2017 ), and miR-27b inhibited the level of MCP1 in IL-17 treated H9C2 cells (Huang et al, 2016 ). These results indicate that CVB3-induced inflammation was regulated by miRNAs targeted inflammatory signaling pathways.…”