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Status |
Public on Oct 16, 2018 |
Title |
Integrative analysis of transcriptomics and clinical data uncovers the tumorsuppressive activity of MITF in prostate cancer |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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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Overall design |
doxycycline-treated and untreated PC3 cells
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Contributor(s) |
Valcarcel-Jimenez L, Macchia A, Martín-Martín N, Cortazar A, Schaub A, Schaub A, Pujana M, Hermanova I, Astobiza I, Trka J, Sutherland J, Barrio R, Aransay AM, Carracedo A, Torrano V |
Citation(s) |
30310055 |
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Submission date |
May 11, 2018 |
Last update date |
Oct 19, 2018 |
Contact name |
Ana Maria Aransay |
E-mail(s) |
amaransay@cicbiogune.es
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Phone |
0034944061325
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Organization name |
CIC bioGUNE
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Department |
Genome Analysis Platform
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Street address |
Parque tecnologico de Bizkaia, Building 801-A
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City |
Derio |
State/province |
BIZKAIA |
ZIP/Postal code |
48160 |
Country |
Spain |
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Platforms (1) |
GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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Samples (7)
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Relations |
BioProject |
PRJNA471056 |
Supplementary file |
Size |
Download |
File type/resource |
GSE114345_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
GSE114345_raw.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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