title: MicroRNA- 1 represses Cx43 expression in viral myocarditis.
abstract: MicroRNAs (miRNAs) are increasingly reported to have important roles in diverse biological and pathological processes. Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the miR-1 function in the heart are only beginning to emerge. In this study, we investigated miR-1 expression and its potential role in the mouse model of viral myocarditis (VMC). The expression levels of miR-1 and its target gene Connexin 43 (Cx43) were measured by real-time PCR and western blotting, respectively. The miR-1 expression levels were significantly increased in cardiac myocytes from VMC mice in comparison with control samples (relative expression: 10 ± 2.5 vs. 31 ± 7.6, P < 0.05). Among the target genes of miR-1, the expression Cx43 protein was significantly reduced in such mice while there was no significant difference in the its mRNA levels. Our results revealed an inverse correlation between miR-1 levels and Cx43 protein expression in VMC samples. Using a bioinformatics-based approach, we found two identical potential binding sites were found in mouse miR-1 and Cx43 3'- untranslated region, this confirms a possible regulatory role of miR-1. In cultured, miRNA transfected myocardial cells, we show overexpression of miR-1 accompanied by a decrease in Cx43 protein's expression. There was only a slight (not statistically significant) drop in Cx43 mRNA levels. Our results indicate that miR-1 is involved in VMC via post-transcriptional repression of Cx43, and might constitute potentially valuable data for the development of a new approach in the treatment of this disease.
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Xuhui District, Shanghai, People's Republic of China.
authors: Hong-Fei
authors: HF
authors: Xu
authors: Yu-Jie
authors: YJ
authors: Ding
authors: Yi-Wen
authors: YW
authors: Shen
authors: Ai-Min
authors: AM
authors: Xue
authors: Hong-Mei
authors: HM
authors: Xu
authors: Cheng-Liang
authors: CL
authors: Luo
authors: Bei-Xu
authors: BX
authors: Li
authors: Yue-Lin
authors: YL
authors: Liu
authors: Zi-Qin
authors: ZQ
authors: Zhao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D003384:Coxsackievirus Infections / Q000235:genetics* / Q000378:metabolism; D029822:Enterovirus B, Human; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009205:Myocarditis / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D018031:Connexin 43; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D012333:RNA, Messenger