ArticleMolecular endocrinology (Baltimore, Md.)2015
Farnesoid X receptor antagonizes JNK signaling pathway in liver carcinogenesis by activating SOD3.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Targeting the Barriers Driving Immune Exclusion.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Geranylgeraniol promotes osteoblast differentiation and inhibits osteoclastogenesis through MAPK and nuclear receptor signaling.The Journal of biological chemistry · 2026Article
- Transcriptional and Post-Transcriptional Anticholestatic Mechanisms of Obeticholic Acid in Lipopolysaccharide-Induced Cholestasis.Pharmaceutics · 2025Article
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- Article
- Restraint stress promotes nonalcoholic steatohepatitis by regulating the farnesoid X receptor/NLRP3 signaling pathway.Acta biochimica et biophysica Sinica · 2023Article
- Farnesoid X receptor protects against cisplatin-induced acute kidney injury by regulating the transcription of ferroptosis-related genes.Redox biology · 2022Article
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
- Mitochondrial Dysfunction and Oxidative Stress in Liver Transplantation and Underlying Diseases: New Insights and Therapeutics.Transplantation · 2021Review
- Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.Trends in endocrinology and metabolism: TEM · 2021Review
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- The critical role of FXR is associated with the regulation of autophagy and apoptosis in the progression of AKI to CKD.Cell death & disease · 2021Article
- Activation of FXR Suppresses Esophageal Squamous Cell Carcinoma Through Antagonizing ERK1/2 Signaling Pathway.Cancer management and research · 2021Article
- miRNA-382-5p Suppresses the Expression of Farnesoid X Receptor to Promote Progression of Liver Cancer.Cancer management and research · 2021Article
- Farnesoid X receptor: a potential therapeutic target in multiple organs.Histology and histopathology · 2020Review
- EGFR-rich extracellular vesicles derived from highly metastatic nasopharyngeal carcinoma cells accelerate tumour metastasis through PI3K/AKT pathway-suppressed ROS.Journal of extracellular vesicles · 2020Article
- Autophagy and Redox Homeostasis in Parkinson's: A Crucial Balancing Act.Oxidative medicine and cellular longevity · 2020Review
- Multi-omic Pathway and Network Analysis to Identify Biomarkers for Hepatocellular Carcinoma.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2019Article
- Identification of differentially expressed proteins in the gastric mucosal atypical hyperplasia tissue microenvironment.Oncology letters · 2018Article
- Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The farnesoid X receptor (FXR) is a key metabolic and homeostatic regulator in the liver. In the present work, we identify a novel role of FXR in antagonizing c-Jun N-terminal kinase (JNK) signaling pathway in liver carcinogenesis by activating superoxide dismutase 3 (SOD3) transcription. Compared with wild-type mouse liver, FXR(-/-) mouse liver showed elevated JNK phosphorylation. JNK1 deletion suppressed the increase of diethylnitrosamine-induced tumor number in FXR(-/-) mice. These results suggest that JNK1 plays a key role in chemical-induced liver carcinogenesis in FXR(-/-) mice. We found that ligand-activated FXR was able to alleviate H₂O₂or tetradecanoylphorbol acetate-induced JNK phosphorylation in human hepatoblastoma (HepG2) cells or mouse primary hepatocytes. FXR ligand decreased H₂O₂-induced reactive oxygen species (ROS) levels in wild-type but not FXR(-/-) mouse hepatocytes. FXR knockdown abolished the inhibition of 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]-Benzoic acid (GW4064) on JNK phosphorylation and ROS production induced by H₂O₂in HepG2 cells. The gene expression of SOD3, an antioxidant defense enzyme, was increased by FXR activation in vitro and in vivo. An FXR-responsive element, inverted repeat separated by 1 nucleotide in SOD3 promoter, was identified by a combination of transcriptional reporter assays, EMSAs, and chromatin immunoprecipitation assays, which indicated that SOD3 could be a direct FXR target gene. SOD3 knockdown abolished the inhibition of GW4064 on JNK phosphorylation induced by H₂O₂in HepG2 cells. In summary, FXR may regulate SOD3 expression to suppress ROS production, resulting in decreasing JNK activity. These results suggest that FXR, as a novel JNK suppressor, may be an attractive therapeutic target for liver cancer treatment.
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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.