{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:26:03Z","timestamp":1790965563370,"version":"4.1.0"},"reference-count":44,"publisher":"The Company of Biologists","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,15]]},"abstract":"<jats:p>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\u2032 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.<\/jats:p>","DOI":"10.1242\/jcs.067165","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T23:53:31Z","timestamp":1277250811000},"page":"2444-2452","source":"Crossref","is-referenced-by-count":128,"title":["Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy"],"prefix":"10.1242","volume":"123","author":[{"given":"Qing","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Stem Cell Biology and Laboratory of Nucleic Acid and Molecular Medicine, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China"},{"name":"Graduate School of Chinese Academy of Sciences, 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Changhai Hospital, Shanghai 200433, China"},{"name":"Department of Physiology, Second Military Medical University, Shanghai 200433,, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Biology and Laboratory of Nucleic Acid and Molecular Medicine, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China"},{"name":"Graduate School of Chinese Academy of Sciences, 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Biology and Laboratory of Nucleic Acid and Molecular Medicine, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kremneva","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Biology and Laboratory of Nucleic Acid and Molecular Medicine, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Changhai Hospital, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology, Second Military Medical University, Shanghai 200433,, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pekka","family":"Lappalainen","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Second Military Medical University, Shanghai 200433,, China"},{"name":"Department of Physiology and Neurology, Ningxia Medical University, Ningxia 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Wen","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Changhai Hospital, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Jing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Biology and Laboratory of Nucleic Acid and Molecular Medicine, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China"},{"name":"Department of Cardiology, Changhai Hospital, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042521090991700_R1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0092-8674(00)81878-4","article-title":"MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure","volume":"88","author":"Arber","year":"1997","journal-title":"Cell"},{"key":"2021042521090991700_R2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"2021042521090991700_R3","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nm1582","article-title":"MicroRNA-133 controls cardiac hypertrophy","volume":"13","author":"Care","year":"2007","journal-title":"Nat. Med."},{"key":"2021042521090991700_R4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1242\/jcs.041723","article-title":"microRNAs and muscle disorders","volume":"122","author":"Chen","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021042521090991700_R5","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/eurheartj\/ehp573","article-title":"microRNAs in heart disease: putative novel therapeutic targets?","volume":"31","author":"Condorelli","year":"2010","journal-title":"Eur. Heart J."},{"key":"2021042521090991700_R6","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1161\/CIRCULATIONAHA.108.769984","article-title":"Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling","volume":"118","author":"da Costa Martins","year":"2008","journal-title":"Circulation"},{"key":"2021042521090991700_R7","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1038\/sj.emboj.7600310","article-title":"Biological role and structural mechanism of twinfilin-capping protein interaction","volume":"23","author":"Falck","year":"2004","journal-title":"EMBO J."},{"key":"2021042521090991700_R8","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1161\/01.CIR.0000120390.68287.BB","article-title":"Hypertrophy of the heart: a new therapeutic target?","volume":"109","author":"Frey","year":"2004","journal-title":"Circulation"},{"key":"2021042521090991700_R9","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1083\/jcb.142.3.723","article-title":"Regulation of the cortical actin cytoskeleton in budding yeast by twinfilin, a ubiquitous actin monomer-sequestering protein","volume":"142","author":"Goode","year":"1998","journal-title":"J. Cell Biol."},{"key":"2021042521090991700_R10","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1073\/pnas.95.5.2509","article-title":"A simplified system for generating recombinant adenoviruses","volume":"95","author":"He","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042521090991700_R11","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/sj.emboj.7601019","article-title":"Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility","volume":"25","author":"Helfer","year":"2006","journal-title":"EMBO J."},{"key":"2021042521090991700_R12","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1161\/01.RES.86.8.846","article-title":"Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium","volume":"86","author":"Heling","year":"2000","journal-title":"Circ. Res."},{"key":"2021042521090991700_R13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.1136235","article-title":"A hexanucleotide element directs microRNA nuclear import","volume":"315","author":"Hwang","year":"2007","journal-title":"Science"},{"key":"2021042521090991700_R14","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1128\/MCB.01222-08","article-title":"MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes","volume":"29","author":"Ikeda","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"2021042521090991700_R15","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.cell.2004.12.038","article-title":"Involvement of microRNA in AU-rich element-mediated mRNA instability","volume":"120","author":"Jing","year":"2005","journal-title":"Cell"},{"key":"2021042521090991700_R16","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1371\/journal.pbio.0020363","article-title":"Human MicroRNA targets","volume":"2","author":"John","year":"2004","journal-title":"PLoS Biol."},{"key":"2021042521090991700_R17","doi-asserted-by":"crossref","first-page":"31111","DOI":"10.1074\/jbc.M300725200","article-title":"Initiation and transduction of stretch-induced RhoA and Rac1 activation through caveolae: cytoskeletal regulation of ERK translocation","volume":"278","author":"Kawamura","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021042521090991700_R18","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0960-9822(02)00809-6","article-title":"Identification of tissue-specific microRNAs from mouse","volume":"12","author":"Lagos-Quintana","year":"2002","journal-title":"Curr. Biol."},{"key":"2021042521090991700_R19","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.cell.2007.04.040","article-title":"A mammalian microRNA expression atlas based on small RNA library sequencing","volume":"129","author":"Landgraf","year":"2007","journal-title":"Cell"},{"key":"2021042521090991700_R20","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.cub.2005.07.029","article-title":"Methylation protects miRNAs and siRNAs from a 3\u2032-end uridylation activity in Arabidopsis","volume":"15","author":"Li","year":"2005","journal-title":"Curr. Biol."},{"key":"2021042521090991700_R21","doi-asserted-by":"crossref","first-page":"20844","DOI":"10.1073\/pnas.0710558105","article-title":"An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133","volume":"104","author":"Liu","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042521090991700_R22","doi-asserted-by":"crossref","first-page":"20045","DOI":"10.1074\/jbc.M801035200","article-title":"Down-regulation of miR-1\/miR-133 contributes to re-expression of pacemaker channel genes HCN2 and HCN4 in hypertrophic heart","volume":"283","author":"Luo","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2021042521090991700_R23","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1042\/BJ20080608","article-title":"Two biochemically distinct and tissue-specific twinfilin isoforms are generated from the mouse Twf2 gene by alternative promoter usage","volume":"417","author":"Nevalainen","year":"2009","journal-title":"Biochem. J."},{"key":"2021042521090991700_R24","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1091\/mbc.e02-03-0157","article-title":"The two ADF-H domains of twinfilin play functionally distinct roles in interactions with actin monomers","volume":"13","author":"Ojala","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"2021042521090991700_R25","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1073\/pnas.0608725104","article-title":"Structural basis and evolutionary origin of actin filament capping by twinfilin","volume":"104","author":"Paavilainen","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042521090991700_R26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1083\/jcb.200803100","article-title":"Structure of the actin-depolymerizing factor homology domain in complex with actin","volume":"182","author":"Paavilainen","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021042521090991700_R27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1083\/jcb.200106157","article-title":"Interactions with PIP2, ADP-actin monomers, and capping protein regulate the activity and localization of yeast twinfilin","volume":"155","author":"Palmgren","year":"2001","journal-title":"J. Cell Biol."},{"key":"2021042521090991700_R28","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1261\/rna.5248604","article-title":"Fast and effective prediction of microRNA\/target duplexes","volume":"10","author":"Rehmsmeier","year":"2004","journal-title":"RNA"},{"key":"2021042521090991700_R29","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.cell.2006.10.040","article-title":"Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans","volume":"127","author":"Ruby","year":"2006","journal-title":"Cell"},{"key":"2021042521090991700_R30","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.cardiores.2005.01.021","article-title":"Concentric left ventricular remodeling in endothelial nitric oxide synthase knockout mice by chronic pressure overload","volume":"66","author":"Ruetten","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"2021042521090991700_R31","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1161\/01.RES.0000257913.42552.23","article-title":"MicroRNAs play an essential role in the development of cardiac hypertrophy","volume":"100","author":"Sayed","year":"2007","journal-title":"Circ. Res."},{"key":"2021042521090991700_R32","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.cmet.2007.08.014","article-title":"SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B","volume":"6","author":"Sun","year":"2007","journal-title":"Cell Metab."},{"key":"2021042521090991700_R33","doi-asserted-by":"crossref","first-page":"18255","DOI":"10.1073\/pnas.0608791103","article-title":"A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure","volume":"103","author":"van Rooij","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042521090991700_R34","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1126\/science.1139089","article-title":"Control of stress-dependent cardiac growth and gene expression by a microRNA","volume":"316","author":"van Rooij","year":"2007","journal-title":"Science"},{"key":"2021042521090991700_R35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tig.2008.01.007","article-title":"MicroRNAs flex their muscles","volume":"24","author":"van Rooij","year":"2008","journal-title":"Trends Genet."},{"key":"2021042521090991700_R36","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1161\/CIRCRESAHA.108.183426","article-title":"Toward microRNA-based therapeutics for heart disease: the sense in antisense","volume":"103","author":"van Rooij","year":"2008","journal-title":"Circ. Res."},{"key":"2021042521090991700_R37","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1128\/MCB.20.5.1772-1783.2000","article-title":"Mouse A6\/twinfilin is an actin monomer-binding protein that localizes to the regions of rapid actin dynamics","volume":"20","author":"Vartiainen","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2021042521090991700_R38","doi-asserted-by":"crossref","first-page":"34347","DOI":"10.1074\/jbc.M303642200","article-title":"Mammals have two twinfilin isoforms whose subcellular localizations and tissue distributions are differentially regulated","volume":"278","author":"Vartiainen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021042521090991700_R39","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1083\/jcb.200108022","article-title":"Twinfilin is required for actin-dependent developmental processes in Drosophila","volume":"155","author":"Wahlstrom","year":"2001","journal-title":"J. Cell Biol."},{"key":"2021042521090991700_R40","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/eurheartj\/ehq013","article-title":"Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans","volume":"31","author":"Wang","year":"2010","journal-title":"Eur. Heart J."},{"key":"2021042521090991700_R41","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1096\/fj.00-026com","article-title":"beta1 integrin and organized actin filaments facilitate cardiomyocyte-specific RhoA-dependent activation of the skeletal alpha-actin promoter","volume":"15","author":"Wei","year":"2001","journal-title":"FASEB J."},{"key":"2021042521090991700_R42","doi-asserted-by":"crossref","first-page":"e1020","DOI":"10.1371\/journal.pone.0001020","article-title":"miRNA profiling of naive, effector and memory CD8 T cells","volume":"2","author":"Wu","year":"2007","journal-title":"PLoS ONE"},{"key":"2021042521090991700_R43","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature03817","article-title":"Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis","volume":"436","author":"Zhao","year":"2005","journal-title":"Nature"},{"key":"2021042521090991700_R44","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cell.2007.03.030","article-title":"Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2","volume":"129","author":"Zhao","year":"2007","journal-title":"Cell"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/123\/14\/2444\/1583032\/2444.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/123\/14\/2444\/1583032\/2444.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T18:05:53Z","timestamp":1619373953000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/123\/14\/2444\/31216\/Attenuation-of-microRNA-1-derepresses-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,15]]},"references-count":44,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2010,7,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.067165","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2010,7,15]]}}}