Castration-resistant prostate cancer (CRPC) that arise after the failure of androgen blocking therapies cause most of the deaths from prostate cancer (PC), intensifying the need to fully understand CRPC pathophysiology.
A team led by researchers at MD Anderson Cancer Center characterized the transcriptomic differences between untreated PC and locally recurrent CRPC and they report the identification of 145 previously unannotated intergenic long non-coding RNA transcripts (lncRNA) or isoforms that are associated with PC or CRPC. Of the one-third of these transcripts that were specific for CRPC, they defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in ~50% of human PC. Genome-wide expression analysis of a PCAT5-positive PC 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.
Expression level characterization of prostate cancers.
These findings reveal a key molecular determinant of differences between PC and CRPC at the level of the transcriptome. Further, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions.
- Ylipää A, Kivinummi K, Kohvakka A, Annala M, Latonen L, Scaravilli M, Kartasalo K, Leppänen SP, Karakurt S, Seppälä J, Yli-Harja O, Tammela TL, Zhang W, Visakorpi T, Nykter M. (2015) Transcriptome sequencing reveals PCAT5 as a novel ERG-regulated long non-coding RNA in prostate cancer. Cancer Res [Epub ahead of print]. [abstract]