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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jul 28, 2011 |
Title |
LNCaP Prostate Cancer Cells: Control vs. siRNA-PCAT1 Treated |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Transcriptional profiling of LNCaP prostate cancer cells comparing control siRNA-treated LNCaP cells with LNCaP cells treated with siRNAs targeting Prostate Cancer Associated Transcript-1 (PCAT1), an uncharacterized long non-coding RNA.
High-throughput sequencing of polyA+ RNA (RNA-Seq) in human cancer shows remarkable potential to identify both novel disease-specific markers for clinical uses and uncharacterized aspects of tumor biology, particularly non-coding RNA (ncRNA) species. To illustrate this approach, we employed RNA-Seq on a cohort of 102 prostate tissues and cells lines and found that aberrant expression profiles of novel tissue-specific ncRNAs distinguished benign, cancerous, and metastatic tumors. Among these, a novel prostate-cancer specific ncRNA (termed PCAT-1) defined a subset of aggressive cancers with low expression of the epigenetic regulator EZH2, a component of the Polycomb Repressive Complex 2 (PRC2) commonly upregulated in metastatic cancers. In vitro assays for core PRC2 genes indicated that the PRC2 complex directly binds and represses PCAT-1, and that the PCAT-1 transcript reciprocally binds PRC2, suggesting a regulatory feedback mechanism. Importantly, knockdown of PCAT-1 in cells with high levels of endogenous PCAT-1 transcript showed changes in cell proliferation and transcriptional regulation of several key biological processes, including cell cycle. Finally, we showed that ncRNA expression signatures, including PCAT-1, were effective for the non-invasive detection of prostate cancer, and that high ncRNA expression signature values correlate with high-grade histology. The findings presented herein establish the utility of RNA-Seq to comprehensively identify unannotated ncRNAs that define human disease states and characterize PCAT-1 as a novel regulator of cell proliferation mechanistically linked to PRC2 and contributory to translational clinical tests for prostate cancer.
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Overall design |
Two-condition experiment: Control-siRNA-treated versus PCAT1-siRNA-treated LNCaP cells. Biological replicates: 3 control replicates, 3 treatment replicates.
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Contributor(s) |
Iyer MK, Prensner J, Chinnaiyan AM, Cao X, Jing X |
Citation(s) |
21804560 |
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Submission date |
Jun 10, 2011 |
Last update date |
Feb 22, 2018 |
Contact name |
Matthew Iyer |
E-mail(s) |
mkiyer@med.umich.edu
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Phone |
7346154503
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Organization name |
University of Michigan
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Department |
Michigan Center for Translational Pathology
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Lab |
Chinnaiyan Lab
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Street address |
5316 CCGC 0940 1400 E. Medical Center Drive
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City |
Ann Arbor |
State/province |
MI |
ZIP/Postal code |
48109-0940 |
Country |
USA |
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Platforms (1) |
GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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Samples (9)
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GSM740115 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-2, rep 1 |
GSM740116 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-2, rep 2 |
GSM740117 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-2, rep 3 |
GSM740118 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-3, rep 1 |
GSM740119 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-3, rep 2 |
GSM740120 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-3, rep 3 |
GSM740121 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-4, rep 1 |
GSM740122 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-4, rep 2 |
GSM740123 |
LNCaP Cell Line, Control siRNA versus PCAT1-siRNA-4, rep 3 |
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This SubSeries is part of SuperSeries: |
GSE31728 |
Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression |
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Relations |
BioProject |
PRJNA155331 |
Supplementary file |
Size |
Download |
File type/resource |
GSE29886_RAW.tar |
133.6 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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