Show simple item record

dc.contributor.authorVera, Olga
dc.contributor.authorJimenez, Julia
dc.contributor.authorPernia, Olga
dc.contributor.authorRodriguez-Antolin, Carlos
dc.contributor.authorRodriguez, Carmen
dc.contributor.authorSanchez-Cabo, Fatima 
dc.contributor.authorSoto, Javier
dc.contributor.authorRosas, Rocío
dc.contributor.authorLopez-Magallon, Sara
dc.contributor.authorEsteban Rodriguez, Isabel
dc.contributor.authorDopazo, Ana 
dc.contributor.authorRojo, Federico
dc.contributor.authorBelda-Iniesta, Cristobal 
dc.contributor.authorAlvarez, Rafael
dc.contributor.authorValentin, Jaime
dc.contributor.authorBenitez, Javier 
dc.contributor.authorPerona, Rosario
dc.contributor.authorDe Castro, Javier
dc.contributor.authorIbanez de Caceres, Inmaculada
dc.date.accessioned2019-02-11T07:57:36Z
dc.date.available2019-02-11T07:57:36Z
dc.date.issued2017
dc.identifier.citationTheranostics. 2017; 7(17):4118-4134es_ES
dc.identifier.issn1838-7640es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7154
dc.description.abstractOne 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.sponsorshipFIS (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.isoenges_ES
dc.publisherIvyspring International Publisheres_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectCisplatin-resistancees_ES
dc.subjectDNA methylationes_ES
dc.subjectMAFGes_ES
dc.subjectcancer.es_ES
dc.subjectmiR-7es_ES
dc.subject.meshAdolescent es_ES
dc.subject.meshAdult es_ES
dc.subject.meshAged es_ES
dc.subject.meshAged, 80 and over es_ES
dc.subject.meshAntineoplastic Agents es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCisplatin es_ES
dc.subject.meshDNA Methylation es_ES
dc.subject.meshDrug Resistance, Neoplasm es_ES
dc.subject.meshEpigenesis, Genetices_ES
dc.subject.meshFemale es_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMafG Transcription Factor es_ES
dc.subject.meshMicroRNAs es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshNeoplasm Recurrence, Locales_ES
dc.subject.meshOvarian Neoplasms es_ES
dc.subject.meshRepressor Proteins es_ES
dc.subject.meshYoung Adult es_ES
dc.titleDNA Methylation of miR-7 is a Mechanism Involved in Platinum Response through MAFG Overexpression in Cancer Cellses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial 4.0 Internacional*
dc.identifier.pubmedID29158814es_ES
dc.format.volume7es_ES
dc.format.number17es_ES
dc.format.page4118-4134es_ES
dc.identifier.doi10.7150/thno.20112es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderColciencias (Colombia)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1838-7640es_ES
dc.relation.publisherversionhttps://doi.org/10.7150/thno.20112es_ES
dc.identifier.journalTheranosticses_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Bioinformáticaes_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Genómicaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI12/00386es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI12/01463es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/01495es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI15/00186es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CP14/00008es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial 4.0 Internacional
This item is licensed under a: Atribución-NoComercial 4.0 Internacional