Integrative analysis of transcriptomics and clinical data uncovers the tumor- suppressive activity of MITF in prostate cancer

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10381172" target="_blank" >RIV/00216208:11130/18:10381172 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1038/s41419-018-1096-6" target="_blank" >https://doi.org/10.1038/s41419-018-1096-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41419-018-1096-6" target="_blank" >10.1038/s41419-018-1096-6</a>

Result language

angličtina

Original language name

Integrative analysis of transcriptomics and clinical data uncovers the tumor- suppressive activity of MITF in prostate cancer

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NV15-28848A" target="_blank" >NV15-28848A: Targeting specific metabolic pathways to sensitize leukemic patients to L-asparaginase treatment</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell death &amp; disease

ISSN

2041-4889

e-ISSN

—

Volume of the periodical

9

Issue of the periodical within the volume

October

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

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UT code for WoS article

000447236500001

EID of the result in the Scopus database

2-s2.0-85054773948