title: MicroRNA-19b Downregulates Gap Junction Protein Alpha1 and Synergizes with MicroRNA-1 in Viral Myocarditis.
abstract: Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction protein α1 (GJA1) in VMC. In this study, miR-19b was found to be significantly upregulated using the microarray analysis in a mouse model of VMC, and overexpression of miR-19b led to irregular beating pattern in human cardiomyocytes derived from the induced pluripotent stem cells (hiPSCs-CMs). The upregulation of miR-19b was associated with decreased GJA1 in vivo. Furthermore, a miR-19b inhibitor increased, while its mimics suppressed the expression of GJA1 in HL-1 cells. When GJA1 was overexpressed, the miR-19b mimics-mediated irregular beating was reversed in hiPSCs-CMs. In addition, the effect of miR-19b on GJA1 was enhanced by miR-1 in a dose-dependent manner. These data suggest miR-19b contributes to irregular beating through regulation of GJA1 by cooperating with miR-1. Based on the present and our previous studies, it could be indicated that miR-19b and miR-1 might be critically involved in cardiac arrhythmia associated with VMC.
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 13111010032@fudan.edu.cn.
authors.forename: Junyi
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. amxue@fudan.edu.cn.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xue
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 11111010016@fudan.edu.cn.
authors.forename: Liliang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. libeixu@fudan.edu.cn.
authors.forename: Beixu
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 12111010086@fudan.edu.cn.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. shenyiwen@fudan.edu.cn.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. sunning@fudan.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. chenruizhenzs@gmail.com.
authors.forename: Ruizhen
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Soochow University, Suzhou 215123, China. whhongfei@sina.com.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. zqzhao@shmu.edu.cn.
authors.forename: Ziqin
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009205:Myocarditis / Q000235:genetics / Q000821:virology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D014777:Virus Diseases / Q000235:genetics*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; C544547:MIRN1 microRNA, human; C549214:MIRN19A microRNA, human; D035683:MicroRNAs
keywords: gap junction; miR-1; miR-19b; microRNA; viral myocarditis