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Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy.
- Source :
-
Journal of cell science [J Cell Sci] 2010 Jul 15; Vol. 123 (Pt 14), pp. 2444-52. Date of Electronic Publication: 2010 Jun 22. - Publication Year :
- 2010
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Abstract
- MicroRNAs are involved in several aspects of cardiac hypertrophy, including cardiac growth, conduction, and fibrosis. However, their effects on the regulation of the cardiomyocyte cytoskeleton in this pathological process are not known. Here, with microRNA microarray and small RNA library sequencing, we show that microRNA-1 (miR-1) is the most abundant microRNA in the human heart. By applying bioinformatic target prediction, a cytoskeleton regulatory protein twinfilin-1 was identified as a potential target of miR-1. Overexpression of miR-1 not only reduced the luciferase activity of the reporter containing the 3' untranslated region of twinfilin-1 mRNA, but also suppressed the endogenous protein expression of twinfilin-1, indicating that twinfilin-1 is a direct target of miR-1. miR-1 was substantially downregulated in the rat hypertrophic left ventricle and phenylephrine-induced hypertrophic cardiomyocytes, and accordingly, the protein level of twinfilin-1 was increased. Furthermore, overexpression of miR-1 in hypertrophic cardiomyocytes reduced the cell size and attenuated the expression of hypertrophic markers, whereas silencing of miR-1 in cardiomyocytes resulted in the hypertrophic phenotype. In accordance, twinfilin-1 overexpression promoted cardiomyocyte hypertrophy. Taken together, our results demonstrate that the cytoskeleton regulatory protein twinfilin-1 is a novel target of miR-1, and that reduction of miR-1 by hypertrophic stimuli induces the upregulation of twinfilin-1, which in turn evokes hypertrophy through the regulation of cardiac cytoskeleton.
- Subjects :
- Animals
Animals, Newborn
Cardiomegaly chemically induced
Cardiomegaly genetics
Computational Biology
Gene Expression Profiling
Humans
Mice
MicroRNAs genetics
Microarray Analysis
Microfilament Proteins genetics
Myocytes, Cardiac drug effects
Myocytes, Cardiac immunology
Myocytes, Cardiac pathology
NIH 3T3 Cells
Phenylephrine pharmacology
Protein Binding drug effects
Protein-Tyrosine Kinases genetics
Rats
Rats, Sprague-Dawley
Transgenes genetics
Cardiomegaly metabolism
Cytoskeleton metabolism
MicroRNAs metabolism
Microfilament Proteins metabolism
Myocytes, Cardiac metabolism
Protein-Tyrosine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 123
- Issue :
- Pt 14
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 20571053
- Full Text :
- https://doi.org/10.1242/jcs.067165