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

By John R. Prensner, Matthew K. Iyer, O. A. Balbin, S. Dhanasekaran, Q. Cao, J. Brenner, B. Laxman, I. Asangani, Catherine S. Grasso, Hal D. Kominsky and 10 more. Nature Biotechnology, 2011

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Noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease and to reveal uncharacterized aspects of tumor biology. Here we discover 121 unannotated prostate cancer–associated ncRNA transcripts (PCATs) by ab initio assembly of high-throughput sequencing of polyA+ RNA (RNA-Seq) from a cohort of 102 prostate tissues and cells lines. We characterized one ncRNA, PCAT-1, as a prostate-specific regulator of cell proliferation and show that it is a target of the Polycomb Repressive Complex 2 (PRC2). We further found that patterns of PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1–repressed target genes. Taken together, our findings suggest that PCAT-1 is a transcriptional repressor implicated in a 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.

Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/61d1fbeeade46bbf558f3bfa614a57f7507cf668

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Citations in the corpus

The emergence of lncRNAs in cancer biology (2011, background): “Dysregulated expression of lncRNAs in cancer marks the spectrum of disease progression (9) and may serve as an independent predictor for patient outcomes (28).”
Long Noncoding RNAs: Past, Present, and Future (2013, background): “For example, a recent RNA-Seq study in prostate cancer tissues and cell lines uncovered a lncRNA, PCAT-1, that promotes cell proliferation and is a target of PRC2 regulation (while also possibly interacting with PRC2 itself) (Prensner et al. 2011).”
Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy (2013, background): “Two components of this signature correspond to previously reported long ncRNAs differentially expressed in prostate cancer: Prostate Cancer Associated Transcript (PCAT) 32 and PCAT-80 [33].”
Comprehensive Genomic Characterization of Long Non-Coding RNAs across Human Cancers (2015, background): “In addition to the fact that they are highly deregulated in tumors (Akrami et al., 2013; Calin et al., 2007; Du et al., 2013; Iyer et al., 2015; Kim et al., 2014; Li et al., 2015; Ling et al., 2013; Prensner et al., 2011; Trimarchi et al., 2014; Xing et al., 2014), lncRNAs have been found to act as ”
LncRNA-mediated regulation of cell signaling in cancer (2017, background): “PCAT-1 functions as a prostate-specific regulator of cell proliferation and it has been implicated in a subset of prostate cancer patients (Prensner et al 2011).”
NONCODE v3.0: integrative annotation of long noncoding RNAs (2011, methodology): “Computational methods including ORF-Predictor and BLASTP pipeline (7) identified 5446 lncRNAs in the human genome, 1859 lncRNAs were found throughout the human genome by high-throughput sequencing across a prostate cancer cohort (8) and a reference catalog of 8195 lincRNAs were founded using RNA-seq”
OncodriveFML: a general framework to identify coding and non-coding regions with cancer driver mutations (2016, methodology): “We next employed OncodriveFML to explore the potential of a group of lncRNAs collected from the literature the biological functions of which have been established [34–36] (Additional file 4).”