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E-GEOD-29886 - LNCaP Prostate Cancer Cells: Control vs. siRNA-PCAT1 Treated

Status
Released on 27 July 2011, last updated on 2 May 2014
Organism
Homo sapiens
Samples (18)
Array (1)
Protocols (9)
Description
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. Two-condition experiment: Control-siRNA-treated versus PCAT1-siRNA-treated LNCaP cells. Biological replicates: 3 control replicates, 3 treatment replicates.
Experiment type
transcription profiling by array 
Contacts
Matthew Iyer <mkiyer@med.umich.edu>, Arul M Chinnaiyan, John Prensner, Matthew K Iyer, Xiaojun Jing, Xuhong Cao
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-29886.idf.txt
Sample and data relationshipE-GEOD-29886.sdrf.txt
Raw data (1)E-GEOD-29886.raw.1.zip
Processed data (1)E-GEOD-29886.processed.1.zip
Array designA-AGIL-28.adf.txt
R ExpressionSetE-GEOD-29886.eSet.r
Links