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Several of these lost miRNAs have tumor-suppressor features, so strategies to restore their expression globally in malignancies would be a welcome addition to the current therapeutic arsenal against cancer. Herein, we show that the small molecule enoxacin, a fluoroquinolone used as an antibacterial compound, enhances the production of miRNAs with tumor suppressor functions by binding to the miRNA biosynthesis protein TAR RNA-binding protein 2 (TRBP). The use of enoxacin in human cell cultures and xenografted, orthotopic, and metastatic mouse models reveals a TRBP-dependent and cancer-specific growth-inhibitory effect of the drug. These results highlight the key role of disrupted miRNA expression patterns in tumorigenesis, and suggest a unique strategy for restoring the distorted microRNAome of cancer cells to a more physiological setting.<\/jats:p>","DOI":"10.1073\/pnas.1014720108","type":"journal-article","created":{"date-parts":[[2011,3,2]],"date-time":"2011-03-02T03:35:37Z","timestamp":1299036937000},"page":"4394-4399","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":226,"title":["Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing"],"prefix":"10.1073","volume":"108","author":[{"given":"Sonia","family":"Melo","sequence":"first","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Alberto","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Catia","family":"Moutinho","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Veronica","family":"Davalos","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Riccardo","family":"Spizzo","sequence":"additional","affiliation":[{"name":"M D Anderson Cancer Center"}]},{"given":"Cristina","family":"Ivan","sequence":"additional","affiliation":[{"name":"M D Anderson Cancer Center"}]},{"given":"Simona","family":"Rossi","sequence":"additional","affiliation":[{"name":"M D Anderson Cancer Center"},{"name":"Bioinformatics Core Facility","place":["Switzerland"]}]},{"given":"Fernando","family":"Setien","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Oriol","family":"Casanovas","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Laia","family":"Simo-Riudalbas","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Javier","family":"Carmona","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Jordi","family":"Carrere","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"August","family":"Vidal","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Alvaro","family":"Aytes","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Sara","family":"Puertas","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]}]},{"given":"Santiago","family":"Ropero","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1","place":["Spain"]}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"Harvard Medical School"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Ohio State University"}]},{"given":"George A.","family":"Calin","sequence":"additional","affiliation":[{"name":"M D Anderson Cancer Center"}]},{"given":"Manel","family":"Esteller","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute","place":["Spain"]},{"name":"Institucio Catalana de Recerca i Estudis Avan\u00e7ats","place":["Spain"]}]}],"member":"341","published-online":{"date-parts":[[2011,2,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1379"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.035"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.8.080706.092351"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03702"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510565103"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1840"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0507-582"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1997"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2698"},{"key":"e_1_3_4_11_2","article-title":"Dysregulation of microRNAs in cancer: Playing with fire","author":"Melo SA","year":"2010","unstructured":"SA Melo, M Esteller, Dysregulation of microRNAs in cancer: Playing with fire. 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