Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression

被引：853

作者：

Prensner, John R. ^{[1
]}

Iyer, Matthew K. ^{[1
]}

Balbin, O. Alejandro ^{[1
]}

Dhanasekaran, Saravana M. ^{[1
,2
]}

Cao, Qi ^{[1
]}

Brenner, J. Chad ^{[1
]}

Laxman, Bharathi ^{[3
]}

Asangani, Irfan A. ^{[1
]}

Grasso, Catherine S. ^{[1
]}

Kominsky, Hal D. ^{[1
]}

Cao, Xuhong ^{[1
]}

Jing, Xiaojun ^{[1
]}

Wang, Xiaoju ^{[1
]}

Siddiqui, Javed ^{[1
]}

Wei, John T. ^{[4
]}

Robinson, Daniel ^{[1
]}

Iyer, Hari K. ^{[5
]}

Palanisamy, Nallasivam ^{[1
,2
,6
]}

Maher, Christopher A. ^{[1
,2
]}

Chinnaiyan, Arul M. ^{[1
,2
,4
,6
,7
]}

机构：

[1] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA

[3] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[4] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA

[5] Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA

[6] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA

[7] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 08期

基金：

美国国家卫生研究院;

关键词：

LONG NONCODING RNA; GENE FUSIONS; HUMAN GENOME; POLYCOMB; REVEALS; BREAST; LOCI; BIOMARKER; ELEMENTS; MARKER;

D O I：

10.1038/nbt.1914

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：742 / U134

页数：9

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