{"doi":"10.3390/ijms26083909","title":"Expression of Prooncogenic Nuclear Receptor 4A (NR4A)-Regulated Genes β1-Integrin and G9a Inhibited by Dual NR4A1/2 Ligands","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.","journal":"International Journal of Molecular Sciences","year":2025,"id":543843,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1433791,"name":"Victoria Gatlin","orcid":"0009-0002-5887-2314","position":1,"is_corresponding":false},{"id":1173488,"name":"Shreyan Gupta","orcid":"0000-0002-1904-9862","position":2,"is_corresponding":false},{"id":772828,"name":"Michael L. Salinas","orcid":"0000-0001-5609-3996","position":3,"is_corresponding":false},{"id":1433792,"name":"Selim Romero","orcid":"0000-0002-2401-6272","position":4,"is_corresponding":false},{"id":243189,"name":"James J. Cai","orcid":"0000-0002-8081-6725","position":5,"is_corresponding":false},{"id":241898,"name":"Robert S. Chapkin","orcid":"0000-0002-6515-3898","position":6,"is_corresponding":false},{"id":260421,"name":"Stephen Safe","orcid":"0000-0002-2115-3060","position":7,"is_corresponding":false},{"id":890859,"name":"Lei Zhang","orcid":"0000-0002-7781-3478","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:53:08.338070Z","pmid":"40332813","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}