Early Detection Research Network

PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer.

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.

Araujo JC, Canman CE, Cao Q, Chen W, Chinnaiyan AM, Demichelis F, Feng FY, Han S, Iyer MK, Kitabayashi N, Knudsen KE, Lawrence TS, Logothetis CJ, Ma T, Malik R, Navone N, Pisters LL, Prensner JR, Rubin MA, Sahu A, Tewari AK, Wilder-Romans K

24473064

Cancer Res., 2014, 74 (6)

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