Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer
Antti Ylipää1, Kati Kivinummi1, Annika Kohvakka2
1Department of Signal Processing, Tampere University of Technology, Tampere, Finland. Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
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.
Insights
Researchers identified 145 new long noncoding RNA transcripts in prostate cancer. A novel transcript, PCAT5, drives castration-resistant prostate cancer (CRPC) growth and may offer new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer mortality.
- Understanding CRPC pathophysiology is crucial for developing effective treatments.
- Androgen-blocking therapies often fail, leading to CRPC development.
Purpose of the Study:
- To characterize transcriptomic differences between untreated prostate cancer and CRPC.
- To identify novel molecular players in CRPC development.
- To investigate the role of a newly identified long noncoding RNA (lncRNA) in CRPC.
Main Methods:
- Transcriptomic analysis comparing untreated prostate cancer and CRPC.
- Identification and characterization of novel intergenic long noncoding RNA (lncRNA) transcripts.
- Silencing of a specific lncRNA (PCAT5) and subsequent genome-wide expression analysis.
- In vitro validation of affected cellular processes.
Main Results:
- Identified 145 previously unannotated lncRNA transcripts associated with prostate cancer or CRPC.
- Discovered a novel lncRNA, PCAT5, which is specific to CRPC and a target of the ERG transcription factor.
- PCAT5 silencing altered cell proliferation pathways, impacting cell growth, migration, invasion, colony formation, and apoptosis.
Conclusions:
- PCAT5 is a novel oncogenic lncRNA in ERG-positive prostate cancers.
- PCAT5 plays a key role in CRPC pathophysiology by influencing multiple cellular processes.
- Findings have implications for CRPC biomarker development and novel therapeutic strategies.
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