Evidence map›Paper›PMID 40332813›Full record

ArticleInternational journal of molecular sciences2025

Expression of Prooncogenic Nuclear Receptor 4A (NR4A)-Regulated Genes β1-Integrin and G9a Inhibited by Dual NR4A1/2 Ligands.

Lei Zhang, Victoria Gatlin, Shreyan Gupta, Michael L Salinas, Selim Romero, James J Cai, Robert S Chapkin, Stephen Safe

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2025. 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

8 authors.

Lei ZhangDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Victoria GatlinDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.ORCID 0009-0002-5887-2314
Shreyan GuptaDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-1904-9862
Michael L SalinasCPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0001-5609-3996
Selim RomeroDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-2401-6272
James J CaiDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-8081-6725
Robert S ChapkinCPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA.
Stephen SafeDepartment of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-2115-3060

Funding

Texas A&M Center for Environmental Health Research (TiCER)P30ES029067 · NIEHS · TEXAS A&M UNIVERSITY · PI Sakhila Banu · 2019 to 2026
$13.0M
NR4A1 Antagonists Inhibit Colorectal Cancer Growth and Enhance Immune SurveillanceR01CA269580 · NCI · TEXAS A&M UNIVERSITY · PI MAEN ABDELRAHIM, James Jing Cai · 2023 to 2026
$2.3M
Allen Endowed Chair in Nutrition & Chronic Disease Prevention 0Cancer Prevention & Research Institute of Texas RP230204NCI NIH HHS R01 CA269580NIEHS NIH HHS P30 ES029067NIH HHS 1P30ES029067-28A6NIH HHS 1R01CA269580-26A1Syd Kyle Chair Endowment 0U.S. Department of Defense GW200026
6 · The paper itself

Abstract

Bis-indole-derived compounds including 1,1-bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs bind both orphan nuclear receptors 4A1 (NR4A1) and NR4A2, and DIM-3,5 compounds act as dual receptor inverse agonists and inhibit both NR4A1- and NR4A2-regulated responses. Chromatin immunoprecipitation assays show that β1-integrin and the methyltransferase gene G9a are regulated by both NR4A1 and NR4A2 acting as cofactors for Sp1- and Sp4-dependent gene expression. DIM-3,5 treatment results in the loss of one or more of these nuclear factors from the β1-integrin and G9a promoters. Single-cell and RNAseq analyses show that both receptors regulate common (<10%) and unique genes in SW480 colon cancer cells; however, functional enrichment analysis of the differentially expressed genes converges to several common pathways and gene ontology terms.

Indexed as

Histocompatibility AntigensHistone-Lysine N-MethyltransferaseIntegrin beta1Nuclear Receptor Subfamily 4, Group A, Member 1Nuclear Receptor Subfamily 4, Group A, Member 2Cell Line, TumorGene Expression Regulation, NeoplasticHumansIndolesLigandsPromoter Regions, GeneticEHMT2 protein, humanHistocompatibility AntigensHistone-Lysine N-MethyltransferaseIndolesIntegrin beta1Itgb1 protein, humanLigandsNR4A1 protein, humanNR4A2 protein, humanNuclear Receptor Subfamily 4, Group A, Member 1Nuclear Receptor Subfamily 4, Group A, Member 2NR4A1NR4A2pro-oncogenictargetable

Identifiers

PMID40332813
PMCPMC12028307

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.