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 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.