Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/187802
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

DNA methylation of miR-7 is a mechanism involved in platinum response through MAFG overexpression in cancer cells

AuthorsVera Puente, Olga; Jiménez Hernández, Julia; Pernía, Olga CSIC; Rodriguez-Antolín, Carlos; Rodríguez, Carmen ; Sanchez Cabo, Fatima; Soto Romero, Javier; Rosas, Rocio; Lopez-Magallon, Sara; Esteban Rodriguez, Isabel; Dopazo, Ana; Rojo, Federico; Belda-Iniesta, Cristobal; Alvarez, Rafael; Valentin, Jaime; Benítez, Javier; Perona Abellón, Rosario CSIC ORCID; Castro Carpeño, Javier de; Ibáñez de Cáceres, Inmaculada CSIC ORCID
KeywordsmiR-7
MAFG
DNA methylation
Cisplatin-resistance
Cancer
Issue Date2017
PublisherIvyspring International Publisher
CitationTheranostics 7(17): 4118–4134 (2017)
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.
Publisher version (URL)https://doi.org/10.7150/thno.20112
URIhttp://hdl.handle.net/10261/187802
DOI10.7150/thno.20112
E-ISSN1838-7640
Appears in Collections:(IIBM) Artículos

Files in This Item:
File Description SizeFormat
MAFG.pdf2,43 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

PubMed Central
Citations

23
checked on May 10, 2022

SCOPUSTM   
Citations

31
checked on May 21, 2022

WEB OF SCIENCETM
Citations

31
checked on May 19, 2022

Page view(s)

206
checked on May 21, 2022

Download(s)

99
checked on May 21, 2022

Google ScholarTM

Check

Altmetric

Dimensions


Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.