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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE324984 | GEO | 2026/05/12

REPOSITORIES: GEO

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