ArticleMolecular cancer research : MCR2015
Bile acids regulate nuclear receptor (Nur77) expression and intracellular location to control proliferation and apoptosis.
Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Dysregulation of serum bile acids in liver cancer: a systematic review and meta-analysis.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Cholecystectomy promotes the development of colorectal cancer by the alternation of bile acid metabolism and the gut microbiota.Frontiers in medicine · 2022Pooled it
- The Microbial Bile Acid Metabolite 3-Oxo-LCA Inhibits Colorectal Cancer Progression.Cancer research · 2025Article
- Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2025Review
- Comprehensive analysis of the BID gene to uncover the role of novel alternative splicing isoforms in colon adenocarcinoma: a systematic review of literature and bioinformatics analysis.Cancer cell international · 2025Review
- The Roles and Clinical Significance of Major Hepatic-Derived Metabolites in Hepatocellular Carcinoma.Journal of gastroenterology and hepatology · 2025Review
- Deoxycholic acid induces reactive oxygen species accumulation and promotes colorectal cancer cell apoptosis through the CaMKII-CaWorld journal of gastrointestinal oncology · 2025Article
- Delineating the role of nuclear receptors in colorectal cancer, a focused review.Discover oncology · 2024Review
- Identification of a bile acid and bile salt metabolism-related lncRNA signature for predicting prognosis and treatment response in hepatocellular carcinoma.Scientific reports · 2023Article
- The Role of Gut Microbiota-Derived Lithocholic Acid, Deoxycholic Acid and Their Derivatives on the Function and Differentiation of Immune Cells.Microorganisms · 2023Review
- Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease.World journal of gastroenterology · 2023Review
- A Dual Coverage Monitoring of the Bile Acids Profile in the Liver-Gut Axis throughout the Whole Inflammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis.International journal of molecular sciences · 2023Article
- Vitamin D alleviates non-alcoholic fatty liver diseaseFrontiers in microbiology · 2023Article
- A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.Frontiers in oncology · 2023Article
- Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review.International journal of molecular sciences · 2022Review
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer.Cell death discovery · 2022Article
- Roux-en-Y gastric bypass-induced perturbative changes in microbial communities and metabolic pathways in rats.Frontiers in microbiology · 2022Article
- Nuclear receptor 4A1 (NR4A1) antagonists target paraspeckle component 1 (PSPC1) in cancer cells.Molecular carcinogenesis · 2022Article
- Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer.World journal of gastroenterology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledBile acids (BA) are endogenous agents capable of causing cancer throughout the gastrointestinal (GI) tract. To uncover the mechanism by which BAs exert carcinogenic effects, both human liver and colon cancer cells as well as mouse primary hepatocytes were treated with BAs and assayed for viability, genotoxic stress, and transcriptional response. BAs induced both Nur77 (NR4A1) and proinflammatory gene expression. The intracellular location of BA-induced Nur77 was time dependent; short-term (1-3 hours) exposure induced nuclear Nur77, whereas longer (1-2 days) exposure also increased cytosolic Nur77 expression and apoptosis. Inhibiting Nur77 nuclear export with leptomycin B decreased lithocholic acid (LCA)-induced apoptosis. Extended (7 days) treatment with BA generated resistance to BA with increased nuclear Nur77, viability, and mobility. While, knockdown of Nur77 in BA-resistant cells increased cellular susceptibility to LCA-induced apoptosis. Moreover, in vivo mouse xenograft experiments demonstrated that BA-resistant cells form larger tumors with elevated Nur77 expression compared with parental controls. DNA-binding and gene expression assays identified multiple survival genes (CDK4, CCND2, MAP4K5, STAT5A, and RBBP8) and a proapoptosis gene (BID) as Nur77 targets. Consistently, BA-induced upregulation of the aforementioned genes was abrogated by a lack of Nur77. Importantly, Nur77 was overexpressed in high percentage of human colon and liver cancer specimens, and the intracellular location of Nur77 correlated with elevated serum total BA levels in patients with colon cancer. These data show for the first time that BAs via Nur77 have a dual role in modulating cell survival and death. IMPLICATIONS: These findings establish a direct link between Nur77 and the carcinogenic effect of BAs.
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Registered trials
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.