Document Detail


The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation.
MedLine Citation:
PMID:  19620785     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many microRNAs (miRNAs), posttranscriptional regulators of numerous cellular processes and developmental events, are downregulated in tumors. However, their role in tumorigenesis remains largely unknown. In this work, we examined the role of the muscle-specific miRNAs miR-1 and miR-206 in human rhabdomyosarcoma (RMS), a soft tissue sarcoma thought to arise from skeletal muscle progenitors. We have shown that miR-1 was barely detectable in primary RMS of both the embryonal and alveolar subtypes and that both miR-1 and miR-206 failed to be induced in RMS cell lines upon serum deprivation. Moreover, reexpression of miR-206 in RMS cells promoted myogenic differentiation and blocked tumor growth in xenografted mice by switching the global mRNA expression profile to one that resembled mature muscle. Finally, we showed that the product of the MET proto-oncogene, the Met tyrosine-kinase receptor, which is overexpressed in RMS and has been implicated in RMS pathogenesis, was downregulated in murine satellite cells by miR-206 at the onset of normal myogenesis. Thus, failure of posttranscriptional modulation may underlie Met overexpression in RMS and other types of cancer. We propose that tissue-specific miRNAs such as miR-1 and miR-206, given their ability to modulate hundreds of transcripts and to act as nontoxic differentiating agents, may override the genomic heterogeneity of solid tumors and ultimately hold greater therapeutic potential than single gene-directed drugs.
Authors:
Riccardo Taulli; Francesca Bersani; Valentina Foglizzo; Alessandra Linari; Elisa Vigna; Marc Ladanyi; Thomas Tuschl; Carola Ponzetto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-20
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  119     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-04     Completed Date:  2009-08-27     Revised Date:  2012-06-04    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2366-78     Citation Subset:  AIM; IM    
Affiliation:
Department of Anatomy, Pharmacology and Forensic Medicine, and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle
Cell Differentiation
Cell Line, Tumor
Humans
Mice
MicroRNAs / genetics,  physiology*
Muscle Development / physiology*
Proto-Oncogene Proteins / antagonists & inhibitors,  physiology
Proto-Oncogene Proteins c-met
Receptors, Growth Factor / antagonists & inhibitors,  physiology
Rhabdomyosarcoma / genetics,  pathology,  prevention & control*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/Proto-Oncogene Proteins; 0/Receptors, Growth Factor; EC 2.7.10.1/MET protein, human; EC 2.7.10.1/Proto-Oncogene Proteins c-met
Comments/Corrections
Comment In:
J Clin Invest. 2009 Aug;119(8):2119-23   [PMID:  19620782 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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