PCAT1 Supports Partial AR-V7 Function and Promotes Enzalutamide Resistance in Prostate Cancer.

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Enzalutamide resistance (Enz-R) is a critical hurdle in advanced prostate cancer (PCa) treatment.
• Identifying molecular drivers of Enz-R is essential for developing new therapeutic strategies.

Purpose of the Study:

• To identify and characterize the role of long non-coding RNA PCAT1 in enzalutamide-resistant prostate cancer.

Main Methods:

• Utilized public transcriptomic data, bioinformatic analyses, RNA immunoprecipitation (RIP), and ChIP-qPCR.
• Conducted in vitro and in vivo functional assays in Enz-R PCa models.

Main Results:

• PCAT1 was upregulated in Enz-R PCa models and correlated with adverse clinical features.
• PCAT1 knockdown inhibited Enz-R cell growth and tumor progression in vivo.
• PCAT1 supports AR-V7 signaling and its downstream transcriptional targets, without significantly altering AR-V7 protein levels.

Conclusions:

• PCAT1 promotes Enz-R PCa growth by supporting AR-V7-associated transcriptional outputs.
• PCAT1 represents a potential therapeutic vulnerability in advanced prostate cancer.
• Further investigation into the interplay between high-dose androgen, PCAT1 suppression, and AR-V7 signaling is warranted.