| Literature DB >> 24473064 |
John R Prensner1, Wei Chen, Matthew K Iyer, Qi Cao, Teng Ma, Sumin Han, Anirban Sahu, Rohit Malik, Kari Wilder-Romans, Nora Navone, Christopher J Logothetis, John C Araujo, Louis L Pisters, Ashutosh K Tewari, Christine E Canman, Karen E Knudsen, Naoki Kitabayashi, Mark A Rubin, Francesca Demichelis, Theodore S Lawrence, Arul M Chinnaiyan, Felix Y Feng.
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. ©2014 AACR.Entities:
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Year: 2014 PMID： 24473064 PMCID： PMC4009928 DOI： 10.1158/0008-5472.CAN-13-3159
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701