Transcriptome Sequencing Identifies PCAT-1, a Novel lincRNA Implicated in Prostate Cancer Progression

• Published in: Nature biotechnology 2011-07, Vol.29 (8), p.742-749
• Main Authors: Prensner, John R., Iyer, Matthew K., Balbin, O. Alejandro, Dhanasekaran, Saravana M., Cao, Qi, Brenner, J. Chad, Laxman, Bharathi, Asangani, Irfan, Grasso, Catherine, Kominsky, Hal D., Cao, Xuhong, Jing, Xiaojun, Wang, Xiaoju, Siddiqui, Javed, Wei, John T., Robinson, Daniel, Iyer, Hari K., Palanisamy, Nallasivam, Maher, Christopher A., Chinnaiyan, Arul M.
• Format: Article
• Language: English
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.1914

High-throughput sequencing of polyA+ RNA (RNA-Seq) in human cancer shows remarkable potential to identify both novel markers of disease and uncharacterized aspects of tumor biology, particularly non-coding RNA (ncRNA) species. We employed RNA-Seq on a cohort of 102 prostate tissues and cells lines and performed ab initio transcriptome assembly to discover unannotated ncRNAs. We nominated 121 such Prostate Cancer Associated Transcripts (PCATs) with cancer-specific expression patterns. Among these, we characterized PCAT-1 as a novel prostate-specific regulator of cell proliferation and target of the Polycomb Repressive Complex 2 (PRC2). We further found that high PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1 -repressed target genes. Taken together, the findings presented herein identify PCAT-1 as a novel transcriptional repressor implicated in subset of prostate cancer patients. These findings establish the utility of RNA-Seq to identify disease-associated ncRNAs that may improve the stratification of cancer subtypes.