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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NV15-28848A" target="_blank" >NV15-28848A: Zvýšení citlivosti leukemických pacientů na léčbu L-asparaginázou ovlivněním metabolických drah</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Cell death &amp; disease

ISSN

2041-4889

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000447236500001

EID výsledku v databázi Scopus

2-s2.0-85054773948