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

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

doi:10.3892/etm.2018.6082

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

Authors:
- Yong Zhang
- Lingli Sun
- Hui Sun
- Zhongqin Yu
- Xia Liu
- Xia Luo
- Cuifang Li
- Dongming Sun
- Tao Li
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Affiliations: Cardiology Department, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430015, P.R. China, Department of Pediatrics, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: April 20, 2018 https://doi.org/10.3892/etm.2018.6082
Pages: 5510-5516

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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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1	Wang C, Dong C and Xiong S: IL-33 enhances macrophage M2 polarization and protects mice from CVB3-induced viral myocarditis. J Mol Cell Cardiol. 103:22–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Nguyen VK, Klawonn F, Mikolajczyk R and Hernandez-Vargas EA: Analysis of practical identifiability of a viral infection model. PLoS One. 11:e01675682016. View Article : Google Scholar : PubMed/NCBI
3	Rienks M, Papageorgiou A, Wouters K, Verhesen W, Leeuwen RV, Carai P, Summer G, Westermann D and Heymans S: A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis. Cell Mol Life Sci. 74:1511–1525. 2017. View Article : Google Scholar : PubMed/NCBI
4	Yue-Chun L, Guang-Yi C, Li-Sha G, Chao X, Xinqiao T, Cong L, Xiao-Ya D and Xiangjun Y: The protective effects of ivabradine in preventing progression from viral myocarditis to dilated cardiomyopathy. Front Pharmacol. 7:4082016. View Article : Google Scholar : PubMed/NCBI
5	Márquez-González H, López-Gallegos D, González-Espinosa AM, Zamudio-López JO and Yáñez-Gutiérrez L: Effect of immune therapy in the prognosis of viral myocarditis in pediatric patients. Rev Med Inst Mex Seguro Soc. 54 Suppl 3:S296–S301. 2016.PubMed/NCBI
6	Yu M, Long Q, Li HH, Liang W, Liao YH, Yuan J and Cheng X: IL-9 inhibits viral replication in coxsackievirus B3-induced myocarditis. Front Immunol. 7:4092016. View Article : Google Scholar : PubMed/NCBI
7	An B, Liu X, Li G and Yuan H: Interleukin-37 ameliorates coxsackievirus B3-induced viral myocarditis by modulating the Th17/regulatory T cell immune response. J Cardiovasc Pharmacol. 69:305–313. 2017. View Article : Google Scholar : PubMed/NCBI
8	Alhouayek M and Muccioli GG: COX-2-derived endocannabinoid metabolites as novel inflammatory mediators. Trends Pharmacol Sci. 35:284–292. 2014. View Article : Google Scholar : PubMed/NCBI
9	Hao Y, Gu X, Zhao Y, Greene S, Sha W, Smoot DT, Califano J, Wu TC and Pang X: Enforced expression of miR-101 inhibits prostate cancer cell growth by modulating the COX-2 pathway in vivo. Cancer Prev Res (Phila). 4:1073–1083. 2011. View Article : Google Scholar : PubMed/NCBI
10	Wu T: Diagnostic criteria for viral myocarditis (Revised Draft). Chin J Prac Pediat. 5:3152000.(In Chinese).
11	Casadonte JR, Mazwi ML, Gambetta KE, Palac HL, McBride ME, Eltayeb OM, Monge MC, Backer CL and Costello JM: Risk factors for cardiac arrest or mechanical circulatory support in children with fulminant myocarditis. Pediatr Cardiol. 38:128–134. 2017. View Article : Google Scholar : PubMed/NCBI
12	Simpson KE, Storch GA, Lee CK, Ward KE, Danon S, Simon CM, Delaney JW, Tong A and Canter CE: High frequency of detection by pcr of viral nucleic acid in the blood of infants presenting with clinical myocarditis. Pediatr Cardiol. 37:399–404. 2016. View Article : Google Scholar : PubMed/NCBI
13	Tse G, Yeo JM, Chan YW, Lai ET and Yan BP: What is the arrhythmic substrate in viral myocarditis? Insights from clinical and animal studies. Front Physiol. 7:3082016. View Article : Google Scholar : PubMed/NCBI
14	Grodums EI and Dempster G: The pathogenesis of Coxsackie group B viruses in experimental infection. Can J Microbiol. 8:105–113. 1962. View Article : Google Scholar : PubMed/NCBI
15	Webb SR, Loria RM, Madge GE and Kibrick S: Susceptibility of mice to group B coxsackie virus is influenced by the diabetic gene. J Exp Med. 143:1239–1248. 1976. View Article : Google Scholar : PubMed/NCBI
16	Bardooli F, McAlindon E, Littlejohns B, Suleiman MS, Chiara BD and Baumbach A: TCT-184 Early changes in circulating miRNA 133a are indicative of cardiac remodelling after 3 months in patients presenting with acute ST elevation myocardial infarction. J Am Coll Cardiol. 68:B75–B76. 2016. View Article : Google Scholar
17	Wang Y, Ouyang M, Wang Q and Jian Z: MicroRNA-142-3p inhibits hypoxia/reoxygenationinduced apoptosis and fibrosis of cardiomyocytes by targeting high mobility group box 1. Int J Mol Med. 38:1377–1386. 2016. View Article : Google Scholar : PubMed/NCBI
18	Singh GB, Raut SK, Khanna S, Kumar A, Sharma S, Prasad R and Khullar M: MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy. Mol Cell Biochem. 424:1–11. 2017. View Article : Google Scholar : PubMed/NCBI
19	Liu D, Wang D, Xu Z, Gao J, Liu M, Liu Y, Jiang M and Zheng D: Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage. Age (Dordr). 37:972015. View Article : Google Scholar : PubMed/NCBI
20	Chen K and Rajewsky N: The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 8:93–103. 2007. View Article : Google Scholar : PubMed/NCBI
21	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
22	Liang Y, Zhao Q, Fan L, Zhang Z, Tan B, Liu Y and Li Y: Down-regulation of MicroRNA-381 promotes cell proliferation and invasion in colon cancer through up-regulation of LRH-1. Biomed Pharmacother. 75:137–141. 2015. View Article : Google Scholar : PubMed/NCBI
23	Liang HQ, Wang RJ, Diao CF, Li JW, Su JL and Zhang S: The PTTG1-targeting miRNAs miR-329, miR-300, miR-381 and miR-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/PTTG1 regulation feedback loop. Oncotarget. 6:29413–29427. 2015. View Article : Google Scholar : PubMed/NCBI
24	Xu Y, Ohms SJ, Li Z, Wang Q, Gong G, Hu Y, Mao Z, Shannon MF and Fan JY: Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance. PLoS One. 8:e820622013. View Article : Google Scholar : PubMed/NCBI
25	Chen B, Duan L, Yin G, Tan J and Jiang X: Simultaneously expressed miR-424 and miR-381 synergistically suppress the proliferation and survival of renal cancer cells-Cdc2 activity is up-regulated by targeting WEE1. Clinics (Sao Paulo). 68:825–833. 2013. View Article : Google Scholar : PubMed/NCBI
26	Rothschild SI, Tschan MP, Jaggi R, Fey MF, Gugger M and Gautschi O: MicroRNA-381 represses ID1 and is deregulated in lung adenocarcinoma. J Thorac Oncol. 7:1069–1077. 2012. View Article : Google Scholar : PubMed/NCBI