What question did this study set out to answer?

This research aims to identify the role of CDX1 in regulating PVT1 exon 9 overexpression in aggressive prostate cancer.

April 5, 2026

Abstract 5730: CDX1 binding to the PVT1 exon 9-associated promoter drives oncogenic PVT1 exon 9 overexpression in aggressive prostate cancer

Key Points

This research aims to identify the role of CDX1 in regulating PVT1 exon 9 overexpression in aggressive prostate cancer.
Conducted FIMO analysis for motif discovery in the PVT1 promoter.
Performed DNA methylation profiling of prostate tumor versus adjacent normal tissues.
Used siRNA to silence CDX1 and assess its effect on PVT1 exon 9 expression.
Analyzed CDX1 expression through immunohistochemistry in high-Gleason-grade tumors.
Employed CRISPR base editing to manipulate CDX1 binding in prostate cancer cell lines.
Identified CDX1 binding site within the PVT1 exon 9-associated promoter.
Observed hypomethylation at PEAP correlating with increased PVT1 exon 9 expression.
CDX1 silencing reduced PVT1 exon 9 levels, while its overexpression increased them.
Digital PCR showed significant reduction in PVT1 exon 9 copy number post-CRISPR editing.

Abstract

Abstract This study elucidates a previously uncharacterized epigenetic-transcriptional regulatory axis involving the transcription factor CDX1 and the PVT1 exon 9-associated promoter (PEAP) that governs PVT1 exon 9 overexpression in aggressive prostate cancer. The long noncoding RNA (lncRNA) PVT1, located at the 8q24 oncogenic locus, has been implicated in prostate tumorigenesis and progression; however, the molecular mechanisms underlying its exon-specific transcriptional activation remains obscure. Through in silico motif discovery using FIMO analysis, we identified a high-affinity CDX1 consensus binding site within the PEAP sequence, suggesting a potential transcriptional regulatory role. DNA methylation profiling of matched prostate tumor and adjacent normal tissues from prostate cancer patients demonstrated promoter hypomethylation at PEAP, concomitant with a significant upregulation of PVT1 exon 9. While siRNA-mediated CDX1 silencing in PVT1 exon 9 overexpressing cells (MDA-PCa-2b and C22OH) attenuated PVT1 exon 9 expression, CDX1 overexpression in RWPE-1 cells enhanced PVT1 exon 9 transcription. Immunohistochemical and immunofluorescence analysis corroborated the nuclear localization and elevated expression of CDX1 in high-Gleason-grade tumors, underscoring its role as a transcriptional activator. Using digital PCR, CRISPR-mediated base editing of the CDX1 binding sequence on PEAP in MDA-PCa-2b and C22OH revealed drastic reduction in PVT1 exon 9 copy number compared to scramble. Collectively, these findings delineate a CDX1-PEAP-PVT1 signaling axis that is dependent on CDX1 binding to PEAP, thereby driving oncogenic PVT1 exon 9 overexpression. This mechanistic insight provides a novel framework for understanding PVT1 exon-specific regulation and positions the CDX1-PEAP interaction as a promising molecular target for therapeutic interventions in PVT1 exon 9 overexpressing prostate cancers. Citation Format: Chinedum C. Udekwu, Siti K. Nuraziza, Seidu Adams, Rachel E. Bonnaci, E. Oluwabunmi Olapade-Olaopa, Olorunseun O. Ogunwobi. CDX1 binding to the PVT1 exon 9-associated promoter drives oncogenic PVT1 exon 9 overexpression in aggressive prostate cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5730.

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