Evidence map›Paper›PMID 41542764›Full record

ArticleThe Journal of clinical investigation2026

Reversing enhancer RNA-mediated IKBKE gene repression enables synthetic anticancer immunity in prostate cancer models.

Xiang Li, Rui Sun, Hao Li, Jacob J Orme, Xu Zhang, Yu Hou, Sean S Park, Yu Zhang, Yi He, Liguo Wang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. 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

17 authors.

Xiang LiDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Rui SunDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Hao LiDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jacob J OrmeDepartment of Biochemistry and Molecular Biology, and.
Xu ZhangDepartment of Biochemistry and Molecular Biology, and.
Yu HouDepartment of Pulmonology, Children's Hospital, National Clinical Research Center for Child Health, Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Sean S ParkDepartment of Radiation Oncology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
Yu ZhangDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yi HeThe First Hospital of Jiaxing, Jiaxing, China.
Liguo WangDivision of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
Veronica Rodriguez-BravoDepartment of Biochemistry and Molecular Biology, and.
Josep Domingo-DomenechDepartment of Biochemistry and Molecular Biology, and.
Shancheng RenDepartment of Urology, Changzheng Hospital, Shanghai, China.
Dan XiaDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Guanghou FuDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhankui JiaDepartment of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Haojie HuangDepartment of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunotherapy has been effective in many cancer types but has failed in multiple clinical trials in prostate cancers, with the underlying mechanisms remaining largely unclear. Here, we demonstrate that androgen receptor pathway inhibitor (ARPI) plus irradiation (IR) triggered robust anticancer immunity in prostate cancers in both patients and mice. We show that androgen-activated AR suppressed innate immune signaling by inducing inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) gene repression through HDAC2 interaction with an IKBKE enhancer RNA (IKBKE eRNA, or IKBKE-e). ARPI treatment caused IKBKE derepression and enhanced an IR-induced innate immune response via action of RIG-I and MDA5 dsRNA sensors. IKBKE-e ablation largely enhanced innate immunity in prostate cancer cells in culture and anticancer immunity in mice. Our results revealed AR, HDAC2, and IKBKE eRNA as critical intrinsic immune suppressors in prostate cancer cells, suggesting that rejuvenating inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε) signaling by targeting IKBKE-e is an actionable strategy to elicit synthetic anticancer immunity in immunologically "cold" cancers such as prostate cancer.

Indexed as

Enhancer Elements, GeneticGene Expression Regulation, NeoplasticI-kappa B KinaseImmunity, InnateNeoplasm ProteinsProstatic NeoplasmsRNA, NeoplasmAnimalsBenzamidesCell Line, TumorDEAD Box Protein 58Histone Deacetylase 2HumansMaleMiceReceptors, AndrogenBenzamidesDdx58 protein, mouseDEAD Box Protein 58HDAC2 protein, humanHdac2 protein, mouseHistone Deacetylase 2I-kappa B KinaseIKBKB protein, humanN-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamideNeoplasm ProteinsReceptors, AndrogenRNA, NeoplasmImmunologyInnate immunityOncologyProstate cancerTherapeutics

Identifiers

PMID41542764
PMCPMC12807474

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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.