Prostate cancer is the most prevalent malignancy among men and is driven by multiple factors, including androgen signaling and its receptor. Long non-coding RNAs, such as PVT1, play key roles in cancer, particularly by regulating gene expression. PVT1 is upregulated in several cancer types and has been shown to interact with the androgen receptor in prostate cells. This study investigates how PVT1 contributes to the prostate cancer phenotype under androgen stimulation. Knockdown of PVT1 was achieved using CRISPR-Cas13d in LNCaP prostate cancer cells subjected to androgen (R1881) or vehicle treatment. Cellular proliferation, invasion, and apoptosis rates were assessed, alongside RNA sequencing (RNA-seq) to analyze genome-wide transcriptomic changes. Six epigenetic marks-AR, EZH2, H3K4me1, H3K4me3, H3K27me3, and H3K27ac-were examined using CUT&RUN. PVT1 knockdown led to a significant reduction in cell proliferation and an increase in apoptosis signaling. Oncogenes such as MYC, AKT1, AKT2, cyclins CCNA2, CCNB1, CCNB2, CCNE1, CCNE2 and cyclin-dependent kinases CDK1 and CDK4, which were upregulated under androgen treatment, exhibited a significantly reduced expression following PVT1 knockdown, thereby modulating cancer-associated oncogenic pathways. Epigenetically, PVT1 knockdown markedly decreased the occupancy of transcriptionally activating epigenetic marks-H3K4me1, H3K4me3, and H3K27ac-on oncogenes, regardless of androgen presence. Analysis of enriched transcription factors associated with the altered genes revealed a regulatory network linked to prostate cancer pathogenesis. PVT1 drives a genome-wide epigenetic reprogramming in prostate cells, underscoring the role of PVT1 as a positive regulator of oncogenic pathways in prostate cancer and highlighting PVT1's potential as a therapeutic target.
Berzoti-Coelho et al. (Fri,) studied this question.