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http://hdl.handle.net/2445/121365
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DC Field | Value | Language |
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dc.contributor.author | Prior, Celia | - |
dc.contributor.author | Perez-Gracia, Jose Luis | - |
dc.contributor.author | Garcia Donas, Jesus | - |
dc.contributor.author | Rodriguez-Antona, Cristina | - |
dc.contributor.author | Guruceaga, Elisabeth | - |
dc.contributor.author | Esteban, Emilio | - |
dc.contributor.author | Suarez, Cristina | - |
dc.contributor.author | Castellano, Daniel | - |
dc.contributor.author | González del Alba, Aránzazu | - |
dc.contributor.author | Lozano, Maria Dolores | - |
dc.contributor.author | Carles, Joan | - |
dc.contributor.author | Climent, Miguel Angel | - |
dc.contributor.author | Arranz, José Ángel | - |
dc.contributor.author | Gallardo, Enrique | - |
dc.contributor.author | Puente, Javier | - |
dc.contributor.author | Bellmunt Molins, Joaquim, 1959- | - |
dc.contributor.author | Gurpide, Alfonso | - |
dc.contributor.author | Lopez-Picazo, Jose Maria | - |
dc.contributor.author | Gonzalez Hernandez, Alvaro | - |
dc.contributor.author | Mellado González, Begoña | - |
dc.contributor.author | Martínez, Esther | - |
dc.contributor.author | Moreno, Fernando | - |
dc.contributor.author | Font Pous, Albert | - |
dc.contributor.author | Calvo, Alfonso | - |
dc.date.accessioned | 2018-04-09T12:20:41Z | - |
dc.date.available | 2018-04-09T12:20:41Z | - |
dc.date.issued | 2014-01-24 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/121365 | - |
dc.description.abstract | PURPOSE: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance. METHODS: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance. RESULTS: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance. CONCLUSIONS: We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies. | - |
dc.format.extent | 10 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0086263 | - |
dc.relation.ispartof | PLoS One, 2014, vol. 9, num. 1, p. e86263-e86263 | - |
dc.relation.uri | https://doi.org/10.1371/journal.pone.0086263 | - |
dc.rights | cc-by (c) Prior, Celia et al., 2014 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Micro RNAs | - |
dc.subject.classification | Càncer de ronyó | - |
dc.subject.classification | Marcadors bioquímics | - |
dc.subject.classification | Resistència als medicaments | - |
dc.subject.classification | RNA | - |
dc.subject.classification | Fenotip | - |
dc.subject.other | MicroRNAs | - |
dc.subject.other | Renal cancer | - |
dc.subject.other | Biochemical markers | - |
dc.subject.other | Drug resistance | - |
dc.subject.other | RNA | - |
dc.subject.other | Phenotype | - |
dc.title | Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 642456 | - |
dc.date.updated | 2018-04-09T12:20:41Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24475095 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
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642456.pdf | 1.05 MB | Adobe PDF | View/Open |
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