Evidence map›Paper›PMID 41787526›Full record

ArticleMolecular cancer2026

KDM5B-driven glucose metabolic reprogramming promotes enzalutamide resistance in prostate cancer via the lactate/hnRNPA1 lactylation/AR-V7 axis.

Rui Sun, Yong Huang, Hao He, Qiuchen Li, Linfeng Wang, Gaojie Zhang, Ziling Wei, Yang Cao, Jing Li, Xianmin Wang and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

23 authors.

Rui Sun *Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Yong Huang *Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Hao He *Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Qiuchen Li *Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Linfeng Wang *Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Gaojie Zhang *Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Ziling WeiSchool of Psychiatry, Chongqing Medical University, Chongqing, 401331, China.
Yang CaoThe First Clinical College of Chongqing Medical University, Chongqing, 401331, China.
Jing LiThe First Clinical College of Chongqing Medical University, Chongqing, 401331, China.
Xianmin WangClinical Laboratory Diagnostics, Jiamusi University, Jiamusi, 154007, China.
Fan YangClinical Laboratory Diagnostics, Jiamusi University, Jiamusi, 154007, China.
Wenjun ChenDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Xiang LiDepartment of Clinical Laboratory, Banan Hospital of Chongqing Medical University, Chongqing, 401320, China.
Jiang YuDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Siyuan LiuThe First Clinical College of Chongqing Medical University, Chongqing, 401331, China.
Congfeng LeiThe First Clinical College of Chongqing Medical University, Chongqing, 401331, China.
Yu JiangDepartment of Urology, Baiqiuen First Hospital of Jilin University, Jilin, 130012, China.
Yueqiang PengDepartment of Urology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
Huiyi SuDepartment of respiratory medicine, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Yingying GaoDepartment of Clinical Laboratory, Banan Hospital of Chongqing Medical University, Chongqing, 401320, China. happygaoyingying@163.com.
Weiyang HeDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. 202485@hospital.cqmu.edu.cn.
Lei YangDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. dr.yanglei@outlook.com.
Jiayu LiuDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. urologistliu2022@163.com.

Funding

The Chongqing Postgraduate Scientific Research Innovation Project CYS240289The National Training Program of Innovation and Entrepreneurship for Undergraduates 202510631006The Ph.D. Train Through Research Project of Chongqing CSTB2022BSXM-JCX0061
6 · The paper itself

Abstract

aimsResistance to enzalutamide (Enza) in castration-resistant prostate cancer (CRPC) is linked to poor prognosis. While KDM5B is highly expressed in Enza-resistant CRPC, the mechanisms of resistance remain poorly understood.

methodsWe applied an integrated approach to study KDM5B using bioinformatics analyses of single-cell and multi-omics data, along with in vitro and in vivo validation. We explored mechanisms through lactylation proteomics, CRISPR/Cas9 editing, ChIP, and dual-luciferase reporter assays.

resultsKDM5B induces Enza resistance by epigenetically suppressing PTEN, which in turn activates the PI3K/Akt signaling pathway to upregulate PGK1 and drive metabolic reprogramming and lactate production. Lactate acts as a substrate for p300-mediated lactylation of hnRNPA1 at lysine 179 (K179), stabilizing hnRNPA1 by blocking NEDD4L-mediated ubiquitination and promoting AR-V7 splicing. A potential positive feedback loop enhances this effect: KDM5B activates AR, and AR, in turn, increases KDM5B expression. Inhibiting KDM5B or p300 can reverse Enza resistance in vivo.

conclusionsWe identify a mechanism linking metabolism, epigenetics, and a KDM5B/AR feedback loop in drug resistance. These findings suggest that multi-target strategies may represent a promising approach to overcome Enza resistance in CRPC.

Indexed as

Drug Resistance, NeoplasmGlucoseHeterogeneous Nuclear Ribonucleoprotein A1Jumonji Domain-Containing Histone DemethylasesLactic AcidPhenylthiohydantoinProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantAnimalsBenzamidesCell Line, TumorGene Expression Regulation, NeoplasticHumansMaleMetabolic ReprogrammingMiceBenzamidesenzalutamideGlucoseHeterogeneous Nuclear Ribonucleoprotein A1hnRNPA1 protein, humanJumonji Domain-Containing Histone DemethylasesLactic AcidNitrilesPhenylthiohydantoinAR-V7Enzalutamide resistancehnRNPA1KDM5BLactylationProstate cancer

Identifiers

PMID41787526
PMCPMC12980947

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.