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ChIP and Myc inhibition assays in hepatoma cells demonstrated that both miR clusters are regulated by Myc in an opposite manner. We show that the two miR clusters exert antagonistic effects on cell proliferation and tumorigenicity. Moreover, their combined deregulation cooperated in modulating the hepatic tumor phenotype, implicating stem cell-like regulation of Myc-dependent miRs in poorly differentiated HBs. Importantly, a four-miR signature representative of these clusters efficiently stratified HB patients, and when applied to 241 hepatocellular carcinomas (HCCs), it identified invasive tumors with a poor prognosis. Our data argue that Myc-driven reprogramming of miR expression patterns contributes to the aggressive phenotype of liver tumors originating from hepatic progenitor cells.<\/jats:p>","DOI":"10.1073\/pnas.1009009107","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T02:04:38Z","timestamp":1289268278000},"page":"20471-20476","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":161,"title":["Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer"],"prefix":"10.1073","volume":"107","author":[{"given":"Stefano","family":"Cairo","sequence":"first","affiliation":[{"name":"Oncogenesis and Molecular Virology Unit, Institut Pasteur, 75015 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U579, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Vaccine Research Institute of San Diego, San Diego, CA 92121;"},{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"de Reyni\u00e8s","sequence":"additional","affiliation":[{"name":"Ligue Nationale Contre le Cancer, 75013 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Duroure","sequence":"additional","affiliation":[{"name":"Oncogenesis and Molecular Virology Unit, Institut Pasteur, 75015 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U579, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Dahan","sequence":"additional","affiliation":[{"name":"Oncogenesis and Molecular Virology Unit, Institut Pasteur, 75015 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U579, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9","family":"Redon","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie Pathologiques, Assistance Publique\u2013H\u00f4pitaux de Paris (APHP) H\u00f4pital de Bic\u00eatre, 94275 Le Kremlin-Bic\u00eatre, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Fabre","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie Pathologiques, Assistance Publique\u2013H\u00f4pitaux de Paris (APHP) H\u00f4pital de Bic\u00eatre, 94275 Le Kremlin-Bic\u00eatre, France;"},{"name":"Unit\u00e9 de Pathologie, Assistance Publique\u2013H\u00f4pitaux de Paris (APHP) H\u00f4pital Paul Brousse, Universit\u00e9 Paris-Sud 11, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U785, 94800 Villejuif, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McClelland","sequence":"additional","affiliation":[{"name":"Vaccine Research Institute of San Diego, San Diego, CA 92121;"},{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin W.","family":"Wang","sequence":"additional","affiliation":[{"name":"Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4258; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Annick","family":"Buendia","sequence":"additional","affiliation":[{"name":"Oncogenesis and Molecular Virology Unit, Institut Pasteur, 75015 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U579, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,11,8]]},"reference":[{"key":"e_1_3_4_1_2","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 DP","year":"2004","unstructured":"DP Bartel, MicroRNAs: Genomics, biogenesis, mechanism, and function. 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