Evidence map›Paper›PMID 40677010›Full record

ArticleThe Prostate2025

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

Hye Seung Nam, Andrew Michael Asberry, Xuehong Deng, Sheng Liu, Jiaoti Huang, Chang-Deng Hu, Jun Wan, Michael K Wendt

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Prostate, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Hye Seung NamBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.ORCID 0000-0002-9556-8920
Andrew Michael AsberryBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Xuehong DengBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jiaoti HuangDepartment of Pathology, Duke University School of Medicine, Duke University, Durham, North Carolina, USA.
Chang-Deng HuBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Michael K WendtBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI ANDREW D MESECAR · 1985 to 2026
$43.4M
NCI NIH HHS P30 CA023168NCI NIH HHS P30 CA082709This study was supported by Purdue University Center for Cancer Research and DOD Prostate Cancer Research Program.
6 · The paper itself

Abstract

backgroundNeuroendocrine 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.

methodsHere 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 were followed by analysis of cell viability, neurite growth, and effects on neuroendocrine-related gene transcription using immunofluorescence, immunohistochemistry, and Western blot. PRMT5 and MEP50 protein expression levels were comprehensively analyzed for clinical correlation in NEPC patient prostate tissue samples.

resultsElevated PRMT5 and MEP50 correlated with increased recurrence in prostate cancer patients receiving androgen deprivation therapy. Depletion of PRMT5 and MEP50 prevented neuroendocrine differentiation (NED)-induced by enzalutamide both in vitro and in a xenograft mouse model. Conversely, overexpression of PRMT5 and MEP50 was sufficient to induce NED in prostate cancer cells. Evaluation of a genetically engineered mouse model, in which PRMT5 and MEP50 were overexpressed in the prostate, similarly indicated NEPC development.

conclusionsOur data suggest that PRMT5:MEP50 are regulators of tNEPC. PRMT5/MEP50 expression could serve as a predictive biomarker and therapeutic target for aggressive forms of prostate cancer.

Indexed as

Carcinoma, NeuroendocrineProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantProtein-Arginine N-MethyltransferasesAdaptor Proteins, Signal TransducingAnimalsBenzamidesCell DifferentiationCell Line, TumorHumansMaleMiceNeuroendocrine CellsNitrilesPhenylthiohydantoinTranscription FactorsAdaptor Proteins, Signal TransducingBenzamidesenzalutamideNitrilesPhenylthiohydantoinPRMT5 protein, humanProtein-Arginine N-MethyltransferasesTranscription FactorsWDR77 protein, humandrug resistanceenzalutamideneuroendocrinePRMT5

Identifiers

PMID40677010
PMCPMC12329194

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.