There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Author and article information

Journal

PubMed ID:: 24473064

PMC ID:: 4009928

DOI:: 10.1158/0008-5472.CAN-13-3159

ScienceOpen disciplines: Chemistry

Keywords: 3' Untranslated Regions,Animals,Antineoplastic Agents,pharmacology,BRCA2 Protein,genetics,metabolism,Cell Death,drug effects,Cell Line, Tumor,DNA Damage,Gene Expression Regulation, Neoplastic,Humans,Male,Mice,Mice, SCID,Phthalazines,Piperazines,Poly(ADP-ribose) Polymerases,antagonists & inhibitors,Prostatic Neoplasms,RNA Interference,RNA, Long Noncoding,Recombinational DNA Repair,Xenograft Model Antitumor Assays

Data availability:

ScienceOpen disciplines: Chemistry

Keywords: 3' Untranslated Regions, Animals, Antineoplastic Agents, pharmacology, BRCA2 Protein, genetics, metabolism, Cell Death, drug effects, Cell Line, Tumor, DNA Damage, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, SCID, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerases, antagonists & inhibitors, Prostatic Neoplasms, RNA Interference, RNA, Long Noncoding, Recombinational DNA Repair, Xenograft Model Antitumor Assays

Comments

Comment on this article

scite_

0

Smart Citations

0

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.