Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/172161
Title: Integrative analysis of transcriptomics and clinical data uncovers the tumor- suppressive activity of MITF in prostate cancer
Author: Valcarcel Jimenez, Lorea
Macchia, Alice
Martín Martín, Natalia
Cortazar, Ana Rosa
Schaub Clerigué, Ariane
Pujana Vaquerizo, Mikel
Fernández Ruiz, Sonia
Lacasa Vascasillas, Isabel
Santos Martin, Aida
Loizaga Iriarte, Ana
Unda Urzaiz, Miguel
Hermanova, Ivana
Astobiza, Ianire
Graupera i Garcia-Milà, Mariona
Starkova, Julia
Sutherland, James
Barrio, Rosa
Aransay, Ana M.
Carracedo, Arkaitz
Torrano, Verónica
Keywords: Càncer de pròstata
Regulació genètica
Prostate cancer
Genetic regulation
Issue Date: 11-Oct-2018
Publisher: Nature Publishing Group
Abstract: The dysregulation of gene expression is an enabling hallmark of cancer. Computational analysis of transcriptomics data from human cancer specimens, complemented with exhaustive clinical annotation, provides an opportunity to identify core regulators of the tumorigenic process. Here we exploit well-annotated clinical datasets of prostate cancer for the discovery of transcriptional regulators relevant to prostate cancer. Following this rationale, we identify Microphthalmia-associated transcription factor (MITF) as a prostate tumor suppressor among a subset of transcription factors. Importantly, we further interrogate transcriptomics and clinical data to refine MITF perturbation-based empirical assays and unveil Crystallin Alpha B (CRYAB) as an unprecedented direct target of the transcription factor that is, at least in part, responsible for its tumor-suppressive activity in prostate cancer. This evidence was supported by the enhanced prognostic potential of a signature based on the concomitant alteration of MITF and CRYAB in prostate cancer patients. In sum, our study provides proof-of-concept evidence of the potential of the bioinformatics screen of publicly available cancer patient databases as discovery platforms, and demonstrates that the MITF-CRYAB axis controls prostate cancer biology.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41419-018-1096-6
It is part of: Cell Death & Disease, 2018, vol. 9
URI: http://hdl.handle.net/2445/172161
Related resource: https://doi.org/10.1038/s41419-018-1096-6
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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