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Cancer Res. 2015 Oct 1;75(19):4026-31. doi: 10.1158/0008-5472.CAN-15-0217. Epub 2015 Aug 17.

Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer.

Author information

1
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
2
Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
3
Department of Signal Processing, Tampere University of Technology, Tampere, Finland.
4
Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
5
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland. matti.nykter@uta.fi tapio.visakorpi@uta.fi.
7
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. matti.nykter@uta.fi tapio.visakorpi@uta.fi.

Abstract

Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking therapies cause most of the deaths from prostate cancer, intensifying the need to fully understand CRPC pathophysiology. In this study, we characterized the transcriptomic differences between untreated prostate cancer and locally recurrent CRPC. Here, we report the identification of 145 previously unannotated intergenic long noncoding RNA transcripts (lncRNA) or isoforms that are associated with prostate cancer or CRPC. Of the one third of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in approximately 50% of human prostate cancer. Genome-wide expression analysis of a PCAT5-positive prostate cancer after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential, and apoptosis. Our findings reveal a key molecular determinant of differences between prostate cancer and CRPC at the level of the transcriptome. Furthermore, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions.

PMID:
26282172
DOI:
10.1158/0008-5472.CAN-15-0217
[Indexed for MEDLINE]
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