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A MYC Family Switch: L-MYC Drives and Maintains Neuroendocrine Lineage Programs in Prostate Cancer

GSE324984 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/05/12 Platform GPL34284
Summary
Neuroendocrine prostate cancer (NEPC) is an aggressive and therapy-resistant subtype that emerges through lineage plasticity following inhibition of the androgen receptor (AR) signaling pathway. In this study, MYCL was overexpressed in prostate adenocarcinoma C4-2B cells and knocked down in neuroendocrine prostate cancer NCI-H660 cells to investigate its role in lineage regulation. RNA-sequencing analysis revealed that MYCL overexpression suppresses AR signaling and MYC target signaling while inducing neuroendocrine-like transcriptional reprogramming. In contrast, MYCL knockdown disrupts neuroendocrine lineage identity and restores adenocarcinoma-associated gene expression programs, including reactivation of MYC. These findings suggest that MYCL plays a key role in regulating lineage plasticity and maintaining neuroendocrine transcriptional programs in prostate cancer.
Published in
A MYC family switch: L-MYC drives and maintains neuroendocrine lineage programs in prostate cancer
Sivalingam J, Ballagh K, Cho KH et al. · Neoplasia (New York, N.Y.) 2026 · PMID 42001796 · doi:10.1016/j.neo.2026.101307
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Also filed as BioProject PRJNA1438189 and SRA study SRP684121. Searching any of these in the dataset finder brings you back here.

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