Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer.
Nat Commun
; 11(1): 441, 2020 01 23.
Article
em En
| MEDLINE
| ID: mdl-31974375
ABSTRACT
Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved in disease onset and progression through both androgen receptor-dependent and androgen receptor-independent mechanisms. Despite its oncogenic properties however, the regulation of FOXA1 expression remains unknown. Here, we identify a set of six cis-regulatory elements in the FOXA1 regulatory plexus harboring somatic single-nucleotide variants in primary prostate tumors. We find that deletion and repression of these cis-regulatory elements significantly decreases FOXA1 expression and prostate cancer cell growth. Six of the ten single-nucleotide variants mapping to FOXA1 regulatory plexus significantly alter the transactivation potential of cis-regulatory elements by modulating the binding of transcription factors. Collectively, our results identify cis-regulatory elements within the FOXA1 plexus mutated in primary prostate tumors as potential targets for therapeutic intervention.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Sequências Reguladoras de Ácido Nucleico
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Fator 3-alfa Nuclear de Hepatócito
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Mutação
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article