dc.contributor.author | Vera, Olga | |
dc.contributor.author | Jimenez, Julia | |
dc.contributor.author | Pernia, Olga | |
dc.contributor.author | Rodriguez-Antolin, Carlos | |
dc.contributor.author | Rodriguez, Carmen | |
dc.contributor.author | Sanchez-Cabo, Fatima | |
dc.contributor.author | Soto, Javier | |
dc.contributor.author | Rosas, Rocío | |
dc.contributor.author | Lopez-Magallon, Sara | |
dc.contributor.author | Esteban Rodriguez, Isabel | |
dc.contributor.author | Dopazo, Ana | |
dc.contributor.author | Rojo, Federico | |
dc.contributor.author | Belda-Iniesta, Cristobal | |
dc.contributor.author | Alvarez, Rafael | |
dc.contributor.author | Valentin, Jaime | |
dc.contributor.author | Benitez, Javier | |
dc.contributor.author | Perona, Rosario | |
dc.contributor.author | De Castro, Javier | |
dc.contributor.author | Ibanez de Caceres, Inmaculada | |
dc.date.accessioned | 2019-02-11T07:57:36Z | |
dc.date.available | 2019-02-11T07:57:36Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Theranostics. 2017; 7(17):4118-4134 | es_ES |
dc.identifier.issn | 1838-7640 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7154 | |
dc.description.abstract | One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines. To identify specific candidate genes under miRNA regulation, we assembled "in silico" miRNAs and mRNAs sequences by using ten different algorithms followed by qRT-PCR validation. Functional assays of site-directed mutagenesis and luciferase activity, miRNAs precursor overexpression, silencing by antago-miR and cell viability were performed to confirm their specificity in gene regulation. Results were further explored in 187 primary samples obtained from ovarian tumors and controls. Results: We identified 4 candidates, miR-7, miR-132, miR-335 and miR-148a, which deregulation seems to be a common event in the development of resistance to cisplatin in both tumor types. miR-7 presented specific methylation in resistant cell lines, and was associated with poorer prognosis in ovarian cancer patients. Our experimental results strongly support the direct regulation of MAFG through miR-7 and their involvement in the development of CDDP resistance in human tumor cells. Conclusion: The basal methylation status of miR-7 before treatment may be a potential clinical epigenetic biomarker, predictor of the chemotherapy outcome to CDDP in ovarian cancer patients. To the best of our knowledge, this is the first report linking the regulation of MAFG by miRNA-7 and its role in chemotherapy response to CDDP. Furthermore, this data highlights the possible role of MAFG as a novel therapeutic target for platinum resistant tumors. | es_ES |
dc.description.sponsorship | FIS (ISCIII) and FEDER/FSE funds (PI12/00386, PI12/01463, PI14/01495, PI15/00186, and FEDER/FSE, Una manera de hacer Europa support the study and contracts of I.I.C. and O.V. PTA2012/7141-I funds support OP contract and I.I.C. was financed by the ‘‘Miguel Servet’’ program (CP 14/00008). The authors gratefully acknowledge the Colombian Department for Science, Technology and Innovation (COLCIENCIAS), partially funding this work to J.S. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Ivyspring International Publisher | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.subject | Cisplatin-resistance | es_ES |
dc.subject | DNA methylation | es_ES |
dc.subject | MAFG | es_ES |
dc.subject | Cancer | es_ES |
dc.subject | miR-7 | es_ES |
dc.subject.mesh | Adolescent | es_ES |
dc.subject.mesh | Adult | es_ES |
dc.subject.mesh | Aged | es_ES |
dc.subject.mesh | Aged, 80 and over | es_ES |
dc.subject.mesh | Antineoplastic Agents | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | Cisplatin | es_ES |
dc.subject.mesh | DNA Methylation | es_ES |
dc.subject.mesh | Drug Resistance, Neoplasm | es_ES |
dc.subject.mesh | Epigenesis, Genetic | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | MafG Transcription Factor | es_ES |
dc.subject.mesh | MicroRNAs | es_ES |
dc.subject.mesh | Middle Aged | es_ES |
dc.subject.mesh | Neoplasm Recurrence, Local | es_ES |
dc.subject.mesh | Ovarian Neoplasms | es_ES |
dc.subject.mesh | Repressor Proteins | es_ES |
dc.subject.mesh | Young Adult | es_ES |
dc.title | DNA Methylation of miR-7 is a Mechanism Involved in Platinum Response through MAFG Overexpression in Cancer Cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial 4.0 Internacional | * |
dc.identifier.pubmedID | 29158814 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 17 | es_ES |
dc.format.page | 4118-4134 | es_ES |
dc.identifier.doi | 10.7150/thno.20112 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Colciencias | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1838-7640 | es_ES |
dc.relation.publisherversion | https://doi.org/10.7150/thno.20112 | es_ES |
dc.identifier.journal | Theranostics | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Bioinformática | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Genómica | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CP14/00008 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2012) (2012)/PI12/00386 | |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2012) (2012)/PI12/01463 | |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2014). Modalidad proyectos en salud. (2014)/PI14/01495 | |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2015). Modalidad proyectos en salud. (2015)/PI15/00186 | |