ArticleGut2024
Identification of PRMT5 as a therapeutic target in cholangiocarcinoma.
Article in Gut, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.Cancers · 2026Review
- Protein arginine methyltransferase 5 orchestrates the homeostasis and reconstitution of intestinal stem cell niche via balancing urea cycling.Cell communication and signaling : CCS · 2026Article
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- Trefoil Factor-3 Is a Hypoxia-Triggered Pro-Tumorigenic Factor in Hepatoblastoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Inhibition of PRMT5 triggers synthetic lethality in ARID1A-deficient endometrial cancer by promoting aberrant R-loop accumulation.Molecular cancer · 2026Article
- Transcriptomic profiling of epigenetic regulators and metabolic reprogramming in human cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- PRMT5 highly expressed on CD16 + CD56- natural killer cells is correlated with NK cells exhaustion in colorectal cancer mesenchyme.Cancer immunology, immunotherapy : CII · 2025Article
- FGF21 and APOA1 mRNA-based therapies for the treatment of experimental acute pancreatitis.Journal of translational medicine · 2025Article
- Histone-related gene WDR77 promotes tumor progression through cell cycle regulation in skin cutaneous melanoma.Frontiers in immunology · 2025Article
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Organoids and spheroids: advancedFrontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
31 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified.
objectiveWe characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA.
designWe evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)-an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors-in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms.
resultsPRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions.
conclusionPRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies.
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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 Socratic graph.