title: Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression.
abstract: 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.
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Prensner
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Iyer
authors.forename: O Alejandro
authors.initials: OA
authors.lastname: Balbin
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.forename: J Chad
authors.initials: JC
authors.lastname: Brenner
authors.forename: Bharathi
authors.initials: B
authors.lastname: Laxman
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Asangani
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Grasso
authors.forename: Hal D
authors.initials: HD
authors.lastname: Kominsky
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jing
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Wang
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.forename: Daniel
authors.initials: D
authors.lastname: Robinson
authors.forename: Hari K
authors.initials: HK
authors.lastname: Iyer
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maher
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D016000:Cluster Analysis; D015331:Cohort Studies; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D063146:Polycomb-Group Proteins; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2