PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer.
Cancer Res
; 74(6): 1651-60, 2014 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-24473064
ABSTRACT
Impairment of double-stranded DNA break (DSB) repair is essential to many cancers. However, although mutations in DSB repair proteins are common in hereditary cancers, mechanisms of impaired DSB repair in sporadic cancers remain incompletely understood. Here, we describe the first role for a long noncoding RNA (lncRNA) in DSB repair in prostate cancer. We identify PCAT-1, a prostate cancer outlier lncRNA, which regulates cell response to genotoxic stress. PCAT-1 expression produces a functional deficiency in homologous recombination through its repression of the BRCA2 tumor suppressor, which, in turn, imparts a high sensitivity to small-molecule inhibitors of PARP1. These effects reflected a posttranscriptional repression of the BRCA2 3'UTR by PCAT-1. Our observations thus offer a novel mechanism of "BRCAness" in sporadic cancers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Regulación Neoplásica de la Expresión Génica
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Proteína BRCA2
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Reparación del ADN por Recombinación
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ARN Largo no Codificante
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cancer Res
Año:
2014
Tipo del documento:
Article