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

John R. Prensner, 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. LawrenceArul M. Chinnaiyan, Felix Y. Feng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

185 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1651-1660
Number of pages10
JournalCancer Research
Volume74
Issue number6
DOIs
StatePublished - Mar 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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