PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en réprimant l'expression du gène suppresseur de tumeurs BRCA2, un long ARN non codant (PCAT-1) joue un rôle dans le développement d'un cancer sporadique de la prostate
Impairment of double-stranded DNA break (DSB) repair is essential to many cancers. However, while 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 (HR) 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 post-transcriptional repression of the BRCA2 3'UTR by PCAT-1. Our observations thus offer a novel mechanism of "BRCA-ness" in sporadic cancers.