biostudies-literatureElurbide JBundesministerium für Bildung und ForschungErasmus ProgramFundación M TorresDepartamento de Educación, Gobierno de NavarraERA-NET TRANSCAN-3Fundación Mario LosantosEuropean Cooperation in Science and TechnologyEuropean CommissionUniversidad Complutense de Madrid&apos;la Caixa&apos; FoundationMinisterio de Ciencia, Innovación y Universidades MCINNMinisterio de Sanidad, Política Social e IgualdadDeutsche ForschungsgemeinschaftInstituto de Salud Carlos IIIMinisterio de Ciencia e InnovaciónJuan Serra FoundationFundación Científica Asociación Española Contra el CáncerMax Planck GesellschaftsFundación Eugenio Rodriguez Pascual116-127https://www.ebi.ac.uk/biostudies/studies/S-EPMC12056590biostudies-literatureUnknown74(1)<h4>Background</h4>Cholangiocarcinoma (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.<h4>Objective</h4>We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA.<h4>Design</h4>We 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, proteGutIdentification of PRMT5 as a therapeutic target in cholangiocarcinoma.PMC12056590PID2020-117116RB-I00 CEX2021-001136-SAC23_1/00008Funding for M.A.A, M.G.F-B, C.BCOST Action Precision-BTC-Network CA22125Sara Borrell Contract CD22/00109HORIZON-HLTH-2022-STAYHLTH-02 No 101095679Ramón y Cajal Program contract RYC2018-024475-12022Funding for M.A.A, M. G. F.B, C.BPID2022-136616OB-I00/AEI/10.13039/501100011033Fellowship to LC2021-1-IT02-KA131-HED-000008150 Placedoc fellowshiLiSYM-KREBS, DEEP-HCCFellowship to B.C-UPredoctoral fellowship PREP2022-000609Caixa Impulse Innovation 2023 (CI23-20155)LABAE20011GARCS2022/BMD-7409TRNSC235657AVILTRANSCAN2022-784-024Post-doctoral contract POSTD18014ARECTR285/10-2PID2020-117941RB-I00/AEI/10.13039/501100011033Trautwein CHuch MAldrighetti LLatasa MUKrawczyk MValbuena EWu HSangro BUrman JMMartinez-Chantar MLLopez-Pascual ACubero FJElurbide JBerasain CSchneider KMMariani SCastello-Uribe BAzkargorta MArechederra MMartinez-Perez LAAdan-Villaescusa EAmat IG Fernandez-Barrena MCasadei Gardini AMarin JJGColyn LUriarte IArnes-Benito RAvila MARatti FElortza FfalseIdentification of PRMT5 as a therapeutic target in cholangiocarcinoma.<h4>Background</h4>Cholangiocarcinoma (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.<h4>Objective</h4>We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA.<h4>Design</h4>We 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, prote2024-01-01T00:00:00Z2024 Dec2026-07-15T11:11:44.106Z2026-07-05T03:08:20.325ZS-EPMC120565903926605110.1136/gutjnl-2024-332998