Evidence map›Paper›PMID 39806412›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

AGD1/USP10/METTL13 complexes enhance cancer stem cells proliferation and diminish the therapeutic effect of docetaxel via CD44 m6A modification in castration resistant prostate cancer.

Hong Wang, Chunli Cui, Weiyi Li, Hui Wu, Jianjun Sha, Jiahua Pan, Wei Xue

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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  16. The mMolecular biomedicine · 2025
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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

7 authors.

Hong WangDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chunli CuiDepartment of Special Examinations, Qingdao Women and Children Hospital, Qingdao, China.
Weiyi LiDepartment of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Hui WuDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianjun ShaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shajianjun@renji.com.
Jiahua PanDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. panjiahua@renji.com.
Wei XueDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xuewei@renji.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMost patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes. This study demonstrated that AGD1, derived from prostate cancer stem cells (PCSCs), enhanced the stemness of prostate cancer cells and reduced the therapeutic effect of docetaxel in CRPC.

methodsQuantitative real-time PCR (qPCR) was employed to determine the expression levels of AGD1 and METTL13 mRNAs in PCSCs and exosomes. Protein expression levels were examined using western blots and dot blots. The potential functions of AGD1 and METTL13 in CRPC were investigated through cell proliferation assay, Transwell assay, EdU incorporation assays, Annexin V-FITC/PI staining, and sphere formation assays. To uncover the underlying mechanisms of AGD1, RNA pull-down assay, RIP, co-Immunoprecipitation (co-IP), mass spectrometry (MS), Methylated RNA immunoprecipitation (MeRIP) and single-base elongation and ligation-based qPCR amplification method (SELECT) were performed. The effects of AGD1 and METTL13 on CRPC development and metastasis under docetaxel treatment were analyzed using a xenograft mouse model and an organoid model. Additionally, liposomal-chitosan nanocomplex drug delivery systems were designed to explore AGD1's role in regulating docetaxel treatment resistance in CRPC.

resultsAGD1 expression was upregulated in PCSCs and exosomes. Downregulating AGD1 enhanced the sensitivity of CRPC to docetaxel treatment by inhibiting their stemness, with the reverse also being true. RNA pull-down, combined with MS, co-IP and RIP assays, demonstrated that AGD1 binds to METTL13 and USP10, forming a complex that facilitates METTL13 protein accumulation through USP10-induced deubiquitination. MeRIP assay and SELECT assay revealed that METTL13 transcriptionally controls the mRNA decay of CD44 via m6A methylation. Additionally, this process activates the pSTAT3/PI3K-AKT signaling pathway. Organoid models and liposomal-chitosan nanocomplex drug delivery systems showed that reducing AGD1 expression enhanced the therapeutic effect of docetaxel in CRPC.

conclusionsAGD1 mediates the stemness and apoptosis of PCSCs and promotes docetaxel treatment resistance by enhancing tumor growth and metastasis through USP10/METTL13-mediated CD44 mRNA decay in CRPC.

Indexed as

DocetaxelHyaluronan ReceptorsMethyltransferasesNeoplastic Stem CellsProstatic Neoplasms, Castration-ResistantAnimalsCell Line, TumorCell ProliferationDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeXenograft Model Antitumor AssaysCD44 protein, humanDocetaxelHyaluronan ReceptorsMethyltransferasesAGD1m6AMETTL13UbiquitinationUSP10

Identifiers

PMID39806412
PMCPMC11730809

What OpenQuestion holds

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Registered trials

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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.