期刊
CANCER RESEARCH
卷 74, 期 6, 页码 1651-1660出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-3159
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资金
- Prostate Cancer Foundation
- NIH Prostate Specialized Program of Research Excellence [P50CA69568]
- Department of Defense [PC094231, PC100171]
- Early Detection Research Network [UO1 CA111275]
- Prostate Cancer Foundation-Movember Challenge Award
- U.S. National Institutes of Health [R01CA132874-01A1, R01CA152057]
- National Center for Functional Genomics
- Department of Defense
- Doris Duke Charitable Foundation Clinical Scientist Award
- Howard Hughes Medical Institute
- Department of Defense Fellowship [PC094290, BC100238, PC094725]
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. (C) 2014 AACR.
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