ArticleMolecular cancer research : MCR2019
Inhibition of NR4A1 Promotes ROS Accumulation and IL24-Dependent Growth Arrest in Rhabdomyosarcoma.
Article in Molecular cancer research : MCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Absence of Thioredoxin Domain Containing 5 Improves Glucose Tolerance and Insulin Sensitivity in Male Mice.International journal of molecular sciences · 2026Article
- The redox-sensitive protein HMGB1: intracellular and extracellular roles.Experimental & molecular medicine · 2026Review
- Nuclear Receptor Subfamily 4 Group A Member 1 Exacerbates Cardiac Remodeling by Inhibiting Mitochondrial Function Through the Peroxisome Proliferator-Activated Receptor γ Coactivator-1α/Nuclear Respiratory Factor 1/Transcription Factor A Mitochondrial Axis.Journal of the American Heart Association · 2025Article
- Dual effects of erastin on aggressive osteosarcoma cells: ferroptosis sensitization and anti-ferroptotic gene activation.Cytotechnology · 2025Article
- Exogenous α-Synuclein Induces Oxidative Damage to Dopaminergic Neurons Through p-NMDAR2B/Nur77.Molecular neurobiology · 2025Article
- Biomarker potential of competing endogenous RNA networks in Polycystic Ovary Syndrome (PCOS).Non-coding RNA research · 2024Review
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- The role and mechanism of TXNDC5 in disease progression.Frontiers in immunology · 2024Review
- Oxidative stress impairs the Nur77-Sirt1 axis resulting in a decline in organism homeostasis during aging.Aging cell · 2023Article
- Employing machine learning using ferroptosis-related genes to construct a prognosis model for patients with osteosarcoma.Frontiers in genetics · 2023Article
- The role and mechanism of TXNDC5 in diseases.European journal of medical research · 2022Review
- Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins.Biomedicines · 2022Article
- Therapeutic potential of NR4A1 in cancer: Focus on metabolism.Frontiers in oncology · 2022Review
- Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth.Journal of experimental & clinical cancer research : CR · 2021Article
- Targeting ferroptosis in osteosarcoma.Journal of bone oncology · 2021Review
- The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies.Antioxidants (Basel, Switzerland) · 2020Review
- Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation.Journal of oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear receptor 4A1 (NR4A1, Nur77) is overexpressed in rhabdomyosarcoma (RMS), and inactivation of NR4A1 (siNR4A1) or treatment with the NR4A1 antagonist 1,1-bis(3'-indoly)-1-(p-hydroxy-phenyl)methane (DIM-C-pPhOH) has antiproliferative and proapoptotic effects on RMS cells. However, the mechanism by which NR4A1 inhibition exerts these effects is poorly defined. Here, we report that NR4A1 silencing or inhibition resulted in accumulation of reactive oxygen species (ROS) and ROS-dependent induction of the tumor suppressor-like cytokine IL24 in RMS cells. Mechanistically, NR4A1 was found to regulate the expression of the proreductant genes thioredoxin domain-containing 5 (TXNDC5) and isocitrate dehydrogenase 1 (IDH1), which are downregulated in RMS cells following NR4A1 knockdown or inhibition. Silencing TXNDC5 and IDH1 also induced ROS accumulation and IL24 expression in RMS cells, suggesting that NR4A1 antagonists mediate their antiproliferative and apoptotic effects through modulation of proreductant gene expression. Finally, cotreatment with the antioxidant glutathione or IL24-blocking antibody reversed the effects of NR4A1 inhibition, demonstrating the importance of both ROS and IL24 in mediating the cellular responses. IMPLICATIONS: Overall, these data elucidate the mechanism by which NR4A1 inhibition functions to inhibit the proliferation, survival, and migration of RMS cells.
Indexed as
Identifiers
What OpenQuestion holds
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.