PRMT5:MEP50 Are Mediators of Treatment-Induced Neuroendocrine Differentiation in Prostate Cancer.

ABSTRACT:

Background

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer responsible for an estimated 20%-30% of castration-resistant prostate cancer (CRPC) deaths. While NEPC can arise spontaneously, the majority of these cases emerge as treatment-induced NEPC (tNEPC). Our clinical and computational analyses identified increased expression of protein methyltransferase 5 (PRMT5) and its cofactor methylosome protein 50 (MEP50) in tNEPC.

Methods

Here we generated an in vitro cell culture and mouse model of prostate cancer to recapitulate tNEPC induced upon treatment with the androgen receptor (AR) inhibitor, enzalutamide. The role of PRMT5 and its cofactor MEP50 were determined by overexpression. Depletion of these genes and pharmacological inhibition of PRMT5 w

SUBMITTER: Nam HS 

PROVIDER: S-EPMC12329194 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature