Featured long non-coding RNA – PCAT-1

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, a team led by researchers at the Michigan Center for Translational Pathology describes the first role for a long noncoding RNA (lncRNA) in DSB repair in prostate cancer. They 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. These observations thus offer a novel mechanism of “BRCAness” in sporadic cancers.

• Prensner JR et al. (2014) PCAT-1, a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer. Cancer Res [Epub ahead of print]. [abstract]