Abstract 6729: The role of L-MYC in prostate cancer

Abstract The MYC family of transcription factors, comprising MYC, N-MYC, and L-MYC, regulates essential cellular processes, including proliferation, metabolism, differentiation, and apoptosis. While MYC and N-MYC have been extensively studied in prostate cancer (PCa), the role of L-MYC remains underexplored. To investigate the expression patterns of these MYC family genes across different stages of PCa, we analyzed publicly available mRNA expression data from normal prostate tissues, adenocarcinoma prostate cancer (AdPCa), neuroendocrine prostate cancer (NEPCa), and PCa cell lines representing AdPCa, castration-resistant prostate cancer (CRPCa), and NEPCa (H660). Our analysis revealed elevated MYC expression in AdPCa patients and AdPCa/CRPCa cell lines, whereas N-MYC showed no significant expression across PCa stages. In contrast, L-MYC was prominently expressed in NEPCa patients and the NEPCa cell line H660. RNA-seq data from patient biopsies (PMID: 26855148) further confirmed increased L-MYC levels in CRPCa-NE compared to CRPCa-Adeno. Additionally, neuroendocrine markers (NCAM1, INSM1, ASCL1, and NEUROD1) were co-expressed with L-MYC in NEPCa, underscoring its association with neuroendocrine differentiation. The expression of L-MYC in H660 cells was further validated by RT-qPCR and Western blot. Despite their shared genomic structure and high sequence homology, MYC family genes exhibit mutually exclusive expression patterns in PCa. Transcription factor binding site (TFBS) analysis revealed unique regulatory elements that may contribute to this differential expression, warranting further investigation. Ongoing RNA-seq analysis of L-MYC knockdown in H660 cells aims to identify pathways regulated by L-MYC and provide insights into its potential as a therapeutic target in NEPCa. These findings suggest that L-MYC plays a pivotal role in NEPCa progression and highlight the importance of understanding the regulatory mechanisms driving its unique expression. Citation Format: Jeyaluxmy Sivalingam, Xiuping Yu. The role of L-MYC in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6729.