Back to Search
Start Over
Over-expression of microRNA-1 causes arrhythmia by disturbing intracellular trafficking system.
- Source :
-
Scientific reports [Sci Rep] 2017 Apr 11; Vol. 7, pp. 46259. Date of Electronic Publication: 2017 Apr 11. - Publication Year :
- 2017
-
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 ([Ca <superscript>2+</superscript> ] <subscript>i</subscript> ). 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.
- Subjects :
- 3' Untranslated Regions
Animals
Biological Transport
Calcium metabolism
Computational Biology methods
Gene Expression Profiling
Gene Ontology
Gene Regulatory Networks
Hypoxia genetics
Hypoxia metabolism
Intracellular Space
Mice
Mice, Transgenic
Models, Biological
Myocardial Ischemia genetics
Myocardial Ischemia metabolism
Myocardial Ischemia physiopathology
Myocytes, Cardiac metabolism
Qa-SNARE Proteins genetics
Qa-SNARE Proteins metabolism
RNA Interference
Transcriptome
Arrhythmias, Cardiac genetics
Arrhythmias, Cardiac physiopathology
Gene Expression
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28397788
- Full Text :
- https://doi.org/10.1038/srep46259