MAFG is a potential therapeutic target to restore chemosensitivity in cisplatin-resistant cancer cells by increasing reactive oxygen species
Author
Vera-Puente, Olga; Rodríguez-Antolín, Carlos; Salgado-Figueroa, Ana; Michalska, Patrycja; Pernia, Olga; Reid, Brett M.; Rosas, RocÍo; García-Guede, Álvaro; Sacristán, Silvia; Jiménez, Julia; Esteban-Rodríguez, Isabel; Martín, M. Elena; Sellers, Thomas A.; León, Rafael; González, VÍctor M.; De Castro, Javier; Ibáñez de Cáceres, InmaculadaEntity
UAM. Departamento de Farmacología; UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ); UAM. Instituto Teófilo Hernando de I+D del Medicamento (ITH)Publisher
Elsevier Inc.Date
2018-06-17Citation
10.1016/j.trsl.2018.06.005
Translational Research: Tthe journal of laboratory and clinical medicine 200 (2018): 1-17
ISSN
1931-5244DOI
10.1016/j.trsl.2018.06.005Funded by
This study was supported by the “Fondo de Investigación Sanitaria-Instituto de Salud Carlos III” [PI15/00186 and CP 08/000689 to I.I.C. ] ; and the European Regional Development Fund/European Social Fund FIS [FEDER/FSE, Una Manera de Hacer Europa] . MINECO funds support O.V., C.R.A. and O.P.contracts through RTC-2015-4362-1 and RTC-2016-5314-1 projects.Editor's Version
https://doi.org/10.1016/j.trsl.2018.06.005Subjects
Chemotherapy; Cisplatin; MicroRNA-7; Non-small-cell lung cancer (NSCLC); Diagnosis; FarmaciaRights
© 2018 The Author(s)Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Adjuvant chemotherapy for solid tumors based on platinum-derived compounds such as cisplatin is the treatment of choice in most cases. Cisplatin triggers signaling pathways that lead to cell death, but it also induces changes in tumor cells that modify the therapeutic response, thereby leading to cisplatin resistance. We have recently reported that microRNA-7 is silenced by DNA methylation and is involved in the resistance to platinum in cancer cells through the action of the musculoaponeurotic fibrosarcoma oncogene family, protein G (MAFG). In the present study, we first confirm the miR-7 epigenetic regulation of MAFG in 44 normal- and/or tumor-paired samples in non–small-cell lung cancer (NSCLC). We also provide translational evidence of the role of MAFG and the clinical outcome in NSCLC by the interrogation of two extensive in silico databases of 2019 patients. Moreover, we propose that MAFG-mediated resistance could be conferred due to lower reactive oxygen species production after cisplatin exposure. We developed specifically selected aptamers against MAFG, with high sensitivity to detect the protein at a nuclear level probed by aptacytochemistry and histochemistry analyses. The inhibition of MAFG activity through the action of the specific aptamer apMAFG6F increased the levels of reactive oxygen species production and the sensitivity to cisplatin. We report first the specific nuclear identification of MAFG as a novel detection method for diagnosis in NSCLC, and then we report that MAFG modulates the redox response and confers cell protection against free radicals generated after platinum administration, thus also being a promising therapeutic target.
Files in this item
Google Scholar:Vera-Puente, Olga
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Rodríguez-Antolín, Carlos
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Salgado-Figueroa, Ana
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Michalska, Patrycja
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Pernia, Olga
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Reid, Brett M.
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Rosas, RocÍo
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García-Guede, Álvaro
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Sacristán, Silvia
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Jiménez, Julia
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Esteban-Rodríguez, Isabel
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Martín, M. Elena
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Sellers, Thomas A.
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León, Rafael
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González, VÍctor M.
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De Castro, Javier
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Ibáñez de Cáceres, Inmaculada
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