• Je něco špatně v tomto záznamu ?

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

L. Valcarcel-Jimenez, A. Macchia, N. Martín-Martín, AR. Cortazar, A. Schaub-Clerigué, M. Pujana-Vaquerizo, S. Fernández-Ruiz, I. Lacasa-Viscasillas, A. Santos-Martin, A. Loizaga-Iriarte, M. Unda-Urzaiz, I. Hermanova, I. Astobiza, M. Graupera, J....

. 2018 ; 9 (10) : 1041. [pub] 20181011

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19045196

Grantová podpora
336343 European Research Council - International

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19045196
003      
CZ-PrNML
005      
20200113105339.0
007      
ta
008      
200109s2018 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/s41419-018-1096-6 $2 doi
035    __
$a (PubMed)30310055
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Valcarcel-Jimenez, Lorea $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
245    10
$a Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer / $c L. Valcarcel-Jimenez, A. Macchia, N. Martín-Martín, AR. Cortazar, A. Schaub-Clerigué, M. Pujana-Vaquerizo, S. Fernández-Ruiz, I. Lacasa-Viscasillas, A. Santos-Martin, A. Loizaga-Iriarte, M. Unda-Urzaiz, I. Hermanova, I. Astobiza, M. Graupera, J. Starkova, J. Sutherland, R. Barrio, AM. Aransay, A. Carracedo, V. Torrano,
520    9_
$a 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.
650    _2
$a zvířata $7 D000818
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a výpočetní biologie $x metody $7 D019295
650    _2
$a regulace genové exprese u nádorů $x genetika $7 D015972
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a myši $7 D051379
650    _2
$a myši nahé $7 D008819
650    _2
$a transkripční faktor spojený s mikroftalmií $x genetika $7 D051739
650    _2
$a buňky PC-3 $7 D000078722
650    _2
$a prognóza $7 D011379
650    _2
$a nádory prostaty $x genetika $x patologie $7 D011471
650    _2
$a transkripční faktory $x genetika $7 D014157
650    _2
$a transkriptom $x genetika $7 D059467
650    _2
$a nádorové supresorové proteiny $x genetika $7 D025521
650    _2
$a alfa-krystaliny - řetězec B $x genetika $7 D038203
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Macchia, Alice $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Martín-Martín, Natalia $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain. CIBERONC, Madrid, Spain.
700    1_
$a Cortazar, Ana Rosa $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain. CIBERONC, Madrid, Spain.
700    1_
$a Schaub-Clerigué, Ariane $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Pujana-Vaquerizo, Mikel $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Fernández-Ruiz, Sonia $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Lacasa-Viscasillas, Isabel $u Department of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
700    1_
$a Santos-Martin, Aida $u Department of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
700    1_
$a Loizaga-Iriarte, Ana $u Department of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
700    1_
$a Unda-Urzaiz, Miguel $u Department of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
700    1_
$a Hermanova, Ivana $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Astobiza, Ianire $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Graupera, Mariona $u Vascular Signalling Laboratory, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199-203, Barcelona, Spain.
700    1_
$a Starkova, Julia $u CLIP-Childhood Leukaemia Investigation. Dept. of Pediatric Hematology and Oncology. Second Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Sutherland, James $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Barrio, Rosa $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Aransay, Ana M $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain.
700    1_
$a Carracedo, Arkaitz $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain. CIBERONC, Madrid, Spain. Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain.
700    1_
$a Torrano, Verónica $u CIC bioGUNE, Bizkaia Technology Park, 801ª bld, 48160, Derio, Bizkaia, Spain. vtorrano@cicbiogune.es. CIBERONC, Madrid, Spain. vtorrano@cicbiogune.es.
773    0_
$w MED00173233 $t Cell death & disease $x 2041-4889 $g Roč. 9, č. 10 (2018), s. 1041
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30310055 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20200109 $b ABA008
991    __
$a 20200113105711 $b ABA008
999    __
$a ok $b bmc $g 1483465 $s 1083869
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 9 $c 10 $d 1041 $e 20181011 $i 2041-4889 $m Cell death & disease $n Cell Death Dis $x MED00173233
GRA    __
$a 336343 $p European Research Council $2 International
LZP    __
$a Pubmed-20200109

Najít záznam

Citační ukazatele

Možnosti archivace