학술논문
PCAT-1, a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer.
Document Type
Article
Author
Prensner, John R.; Wei Chen; Iyer, Matthew K.; Qi Cao; Teng Ma; Sumin Han; Sahu, Anirban; Malik, Rohit; Wilder-Romans, Kari; Navone, Nora; Logothetis, Christopher J.; Araujo, John C.; Pisters, Louis L.; Tewari, Ashutosh K.; Canman, Christine E.; Knudsen, Karen E.; Naoki Kitabayashi; Rubin, Mark A.; Demichelis, Francesca; Lawrence, Theodore S.
Source
Subject
*CANCER genetics
*NON-coding RNA
*TUMOR suppressor genes
*PROSTATE cancer
*CANCER research
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Language
ISSN
0008-5472
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. [ABSTRACT FROM AUTHOR]