Evidence map›Paper›PMID 39954255›Full record

ArticleCell reports2025

CRISPR screening identifies regulators of enhancer-mediated androgen receptor transcription in advanced prostate cancer.

Rachel R Xiang, Shin-Ai Lee, Caroline F Tyndall, Anusha R Bhatia, JuanJuan Yin, Cassandra Singler, Benjamin J Hauk, Matthew P Kipp, David Y Takeda

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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

9 authors.

Rachel R XiangGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shin-Ai LeeGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Caroline F TyndallGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Anusha R BhatiaGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
JuanJuan YinGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cassandra SinglerGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Benjamin J HaukGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Matthew P KippGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
David Y TakedaGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: david.takeda@nih.gov.

Funding

Mechanism of epigenetic activation during disease progressionZIABC011965 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TAKEDA, DAVID · 2020 to 2025
$4.6M
Intramural NIH HHS ZIA BC011965
6 · The paper itself

Abstract

Amplification of the androgen receptor (AR) locus is the most frequent alteration in metastatic castration-resistant prostate cancer (CRPC). Recently, it was discovered that an enhancer of the AR is co-amplified with the AR gene body and contributes to increased AR transcription and resistance to androgen deprivation therapy. However, the mechanism of enhancer activation in advanced disease is unknown. Here, we used CRISPR-Cas9 screening to identify transcription factors that bind to the AR enhancer and modulate enhancer-mediated AR transcription. We demonstrate that HOXB13, GATA2, and TFAP2C bind the AR enhancer in patient-derived xenografts and directly impact features associated with an active chromatin state. Interestingly, the AR enhancer belongs to a set of regulatory elements that require HOXB13 to maintain FOXA1 binding, further delineating the role of HOXB13 in CRPC. This work provides a framework to functionally identify trans-acting factors required for the activation of disease-related noncoding regulatory elements.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsEnhancer Elements, GeneticProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantReceptors, AndrogenTranscription, GeneticAnimalsCell Line, TumorGATA2 Transcription FactorGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaHomeodomain ProteinsHumansMaleMiceAR protein, humanFOXA1 protein, humanGATA2 protein, humanGATA2 Transcription FactorHepatocyte Nuclear Factor 3-alphaHomeodomain ProteinsHOXB13 protein, humanReceptors, AndrogenTFAP2C protein, humanTranscription Factor AP-2androgen receptorCP: CancerCP: Molecular biologyCRISPRCRPCenhancerepigeneticsfunctional genomicsprostate cancer

Identifiers

PMID39954255
PMCPMC11867844

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.