ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Dual Compartmentalization of GSTA4 Suppresses Ferroptosis to Drive Antiandrogen Resistance in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Target FADS1-arachidonic acid-ferroptosis axis: A metabolic bridge linking matrix stiffness to PDAC stemness.Materials today. Bio · 2026Article
- Refining antibiotic cocktail regimens for pseudo-germ-free mice and their impact on gut microbiome and pancreatic tumor proteomics.Journal of advanced research · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Metabolic Landscape of Endometrial Cancer: Insights into Pathway Dysregulation and Metabolic Features.Biomedicines · 2026Article
- Ubiquitination-based Classification and a Prognostic Signature Identify the Role of TRIM21 in Sarcoma Progression.Current medicinal chemistry · 2026Article
- Association of HPGDS Expression with Prognosis and Immune Microenvironment Remodeling in Pancreatic Cancer.Cancer management and research · 2026Article
- TRIM21 suppresses uterine corpus endometrial carcinoma progression by promoting K48 -linked ubiquitination and degradation of SOAT1.Frontiers in immunology · 2026Article
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- INHBA promotes chemoresistance in pancreatic cancer by enhancing CTPS1 stability and mediating pyrimidine metabolism.Cancer cell international · 2025Article
- TRIM21 as a potential prognostic biomarker and therapeutic target affects the growth of pancreatic cancer.Discover oncology · 2025Article
- Network pharmacology and experimental study on the inhibition of glycolysis by amentoflavone in pancreatic cancer.Discover oncology · 2025Article
- OTUB1 antagonizes TRIM21 to induce deubiquitination of SPHK1 and promote the progression of hepatocellular carcinoma.Oncogene · 2025Article
- Review
- MTMR14 depletion aggravates intrapulmonary inflammation and emphysema in experimental COPD through activating macrophage M1 polarization.Respiratory research · 2025Article
- TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Harnessing the gut microbiome to modulate ferroptosis: a metabolic strategy for the treatment of digestive tract cancers.Frontiers in immunology · 2025Review
- TRIM21: a multifaceted regulator in cancer.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Pancreatic cancer (PC) progresses rapidly, and gemcitabine-based chemotherapy has brought only limited efficacy. Identifying key drivers and therapeutic targets holds significant clinical value. In this study, through comprehensive analysis of multiple PC databases, this work identifies TRIM21 as a promising driver mediator. This work further performs loss- and gain-of-function assays for TRIM21, revealing that TRIM21 knockout inhibits tumor proliferation and gemcitabine resistance both in vitro and vivo. Lipidomics reveal that silencing TRIM21 reduce the arachidonic acid production, and inhibit ferroptosis. Mechanically, through proteomics, ubiquitomics, and liquid chromatography-tandem mass spectrometry analysis, the key metabolic enzyme of arachidonic acid -EPHX1 is identified as a downstream substrate of TRIM21. TRIM21 interacts with EPHX1 through its SPRY domain and promotes ubiquitin-mediated degradation of EPHX1 via K33- and K48-linked ubiquitination at the K105 site. Given the targeting potential, this work screens Bezafibrate to block the interaction between TRIM21 and EPHX1 and validates its sensitizing effect. In summary, TRIM21 promotes tumour growth and gemcitabine resistance in PC by inhibiting EPHX1-mediated arachidonic acid metabolism. This provides a novel and promising target for clinical treatment of PC.
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