Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer.
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.
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
Antti
A
Ylipää
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
Kati
K
Kivinummi
Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
Annika
A
Kohvakka
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
Matti
M
Annala
Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
Leena
L
Latonen
Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
Mauro
M
Scaravilli
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
Kimmo
K
Kartasalo
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
Simo-Pekka
SP
Leppänen
Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
Serdar
S
Karakurt
Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
Janne
J
Seppälä
Department of Signal Processing, Tampere University of Technology, Tampere, Finland.
Olli
O
Yli-Harja
Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
Teuvo L J
TL
Tammela
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Wei
W
Zhang
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.
Tapio
T
Visakorpi
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.
Matti
M
Nykter
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011470:Prostatic Hyperplasia / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology*; D000071230:Transcriptional Regulator ERG; D059467:Transcriptome
C072312:ERG protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG