title: Over-expression of microRNA-1 causes arrhythmia by disturbing intracellular trafficking system.
abstract: Dysregulation of intracellular trafficking system plays a fundamental role in the progression of cardiovascular disease. Up-regulation of miR-1 contributes to arrhythmia, we sought to elucidate whether intracellular trafficking contributes to miR-1-driven arrhythmia. By performing microarray analyses of the transcriptome in the cardiomyocytes-specific over-expression of microRNA-1 (miR-1 Tg) mice and the WT mice, we found that these differentially expressed genes in miR-1 Tg mice were significantly enrichment with the trafficking-related biological processes, such as regulation of calcium ion transport. Also, the qRT-PCR and western blot results validated that Stx6, Braf, Ube3a, Mapk8ip3, Ap1s1, Ccz1 and Gja1, which are the trafficking-related genes, were significantly down-regulated in the miR-1 Tg mice. Moreover, we found that Stx6 was decreased in the heart of mice after myocardial infarction and in the hypoxic cardiomyocytes, and further confirmed that Stx6 is a target of miR-1. Meanwhile, knockdown of Stx6 in cardiomyocytes resulted in the impairments of PLM and L-type calcium channel, which leads to the increased resting ([Ca2+]i). On the contrary, overexpression of Stx6 attenuated the impairments of miR-1 or hypoxia on PLM and L-type calcium channel. Thus, our studies reveals that trafficking-related gene Stx6 may regulate intracellular calcium and is involved in the occurrence of cardiac arrhythmia, which provides new insights in that miR-1 participates in arrhythmia by regulating the trafficking-related genes and pathway.
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.|Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.|Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Qiushuang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Yu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.|Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education,), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.|Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D015870:Gene Expression; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D050765:Qa-SNARE Proteins; D002118:Calcium