Integrative Analysis of Transcriptomics and Clinical Data Uncovers the Tumor- Suppressive Activity of MITF in Prostate Cancer

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-a...

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Detalhes bibliográficos
Autores: Valcárcel Jiménez, Lorea, Macchia, Alice, Martín Martín, Natalia, Cortázar, Ana Rosa, Schaub Clerigué, Ariane, Pujana Vaquerizo, Mikel, Fernández Ruiz, Sonia, Lacasa Viscasillas, Isabel, Santos Martín, Aida, Loizaga Iriarte, Ana, Unda Urzaiz, Jesús Miguel, Hermanova, Ivana, Astobiza Pérez, Janire, Graupera, Mariona, Julia, Starkova, Sutherland, James D., Barrio Olano, María Rosa, Aransay Bañares, Ana María, Carracedo Pérez, Arkaitz, Torrano Moya, Verónica
Formato: artículo
Fecha de publicación:2018
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/30345
Acesso em linha:http://hdl.handle.net/10810/30345
Access Level:acceso abierto
Palavra-chave:alpha-B-crystallin
breast-cancer
malignant-melanoma
colorectal-cancer
induced apoptosis
progression
expression
cells
PGC1-alpha
proliferation
Descrição
Resumo: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.

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