TY - JOUR
T1 - PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer
AU - Prensner, John R.
AU - Chen, Wei
AU - Iyer, Matthew K.
AU - Cao, Qi
AU - Ma, Teng
AU - Han, Sumin
AU - Sahu, Anirban
AU - Malik, Rohit
AU - Wilder-Romans, Kari
AU - Navone, Nora
AU - Logothetis, Christopher J.
AU - Araujo, John C.
AU - Pisters, Louis L.
AU - Tewari, Ashutosh K.
AU - Canman, Christine E.
AU - Knudsen, Karen E.
AU - Kitabayashi, Naoki
AU - Rubin, Mark A.
AU - Demichelis, Francesca
AU - Lawrence, Theodore S.
AU - Chinnaiyan, Arul M.
AU - Feng, Felix Y.
PY - 2014/3/15
Y1 - 2014/3/15
N2 - 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 smallmolecule inhibitors of PARP1. These effects reflected a posttranscriptional repression of the BRCA2 30UTR by PCAT-1. Our observations thus offer a novel mechanism of "BRCAness" in sporadic cancers.
AB - 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 smallmolecule inhibitors of PARP1. These effects reflected a posttranscriptional repression of the BRCA2 30UTR by PCAT-1. Our observations thus offer a novel mechanism of "BRCAness" in sporadic cancers.
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U2 - 10.1158/0008-5472.CAN-13-3159
DO - 10.1158/0008-5472.CAN-13-3159
M3 - Article
C2 - 24473064
AN - SCOPUS:84896524997
SN - 0008-5472
VL - 74
SP - 1651
EP - 1660
JO - Cancer Research
JF - Cancer Research
IS - 6
ER -