PCAT-1, a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer

Overview

Journal Cancer Res

Specialty Oncology

Date 2014 Jan 30

PMID 24473064

Citations 149

Authors

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 Lawrence

Arul M Chinnaiyan

Felix Y Feng

Affiliations

Soon will be listed here.

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.

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