{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:25:11Z","timestamp":1789244711234,"version":"build-2803163510"},"reference-count":148,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epigenetic alterations play an increasingly recognized role in carcinogenesis and in the development of resistance to anticancer therapies. Epigenetic enzymes (writers and erasers) and effectors (readers) are largely influenced by the availability of metabolites generated through one-carbon metabolism (OCM), the tricarboxylic acid (TCA) cycle, and acetyl-CoA synthesis (ACS). In this study we examined the expression of epigenetic and metabolic genes to investigate their interplay in cholangiocarcinoma (CCA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      We examined 257 epigenetic genes (EpiGs), 96 metabolic genes (MGs), and 189 rate-limiting enzymes (RLEs) in transcriptomic data from iCCA, eCCA, and normal bile ducts, healthy liver-derived organoids, and CCA tumoroids, alongside prognostic signatures. CRISPR-Cas9 DepMap data evaluated the impact of EpiGs and MGs on cell viability. HuCCT-1 iCCA cells were exposed to hypoxia (1% O\n                      <jats:sub>2<\/jats:sub>\n                      , 24\u00a0h) to assess EpiG responses. Transcriptomic deconvolution characterized EpiGs, MGs, and RLEs expression across four tumor microenvironment (TME) subtypes. Two mouse CCA models (TAZ\/Akt and NICD1\/Akt) underwent RNA-seq, complemented by multi-omic profiling (transcriptomic, proteomic, metabolomic) in TAZ\/Akt livers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Several EpiGs were upregulated in iCCA and eCCA, including writers (\n                      <jats:italic>DNMT1<\/jats:italic>\n                      ,\n                      <jats:italic>EZH2<\/jats:italic>\n                      ,\n                      <jats:italic>SUZ12<\/jats:italic>\n                      ), readers (\n                      <jats:italic>CBX3<\/jats:italic>\n                      ,\n                      <jats:italic>PHF20L1<\/jats:italic>\n                      ,\n                      <jats:italic>SMARCA4<\/jats:italic>\n                      ), and erasers (\n                      <jats:italic>HDAC1<\/jats:italic>\n                      ,\n                      <jats:italic>HDAC3<\/jats:italic>\n                      ,\n                      <jats:italic>KDM5C<\/jats:italic>\n                      ). MGs in OCM, TCA, and ACS pathways were dysregulated (up:\n                      <jats:italic>GART<\/jats:italic>\n                      ,\n                      <jats:italic>IDH2<\/jats:italic>\n                      ,\n                      <jats:italic>TYMS<\/jats:italic>\n                      ; down:\n                      <jats:italic>ALDH1L1<\/jats:italic>\n                      ,\n                      <jats:italic>MAT1A<\/jats:italic>\n                      ,\n                      <jats:italic>SHMT1<\/jats:italic>\n                      ). Integrated analyses identified 27 EpiGs and 8\u00a0MGs whose overexpression predicted poor survival. Subsets of EpiGs, MGs, and RLEs were linked to proliferative, high-recurrence iCCA subclasses. CRISPR screens highlighted 50 EpiGs and 23\u00a0MGs essential for CCA viability. Tumor microenvironment (TME) analyses revealed distinct immune-stromal subclasses with coherent epigenetic-metabolic signatures. In CCA cells, hypoxia induced epigenetic programs that mirrored those in CCA patients. Transcriptomic analyses in human and multi-omic analyses (transcriptomic, metabolomic, and proteomic studies) in mouse CCA livers highlighted rewiring of nucleotide, one-carbon, lipid, and mitochondrial pathways, with evidence of metabolic-epigenetic crosstalk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      EpiGs and MGs are markedly altered in both human and experimental CCA, with several changes particularly enriched in aggressive molecular subclasses associated with poor prognosis. We observed substantial rewiring of epigenetic cofactor-related MG expression in CCAs. Functional assays validated new targets among EpiGs (e.g.,\n                      <jats:italic>CBX3<\/jats:italic>\n                      ,\n                      <jats:italic>CHD4<\/jats:italic>\n                      ,\n                      <jats:italic>DEK<\/jats:italic>\n                      ,\n                      <jats:italic>SMARCA4<\/jats:italic>\n                      , and\n                      <jats:italic>TRIM28<\/jats:italic>\n                      ) and MGs (\n                      <jats:italic>TYMS<\/jats:italic>\n                      and\n                      <jats:italic>IDH2<\/jats:italic>\n                      ) in CCA.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1765945","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:29:59Z","timestamp":1780547399000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic profiling of epigenetic regulators and metabolic reprogramming in human cholangiocarcinoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Amaya","family":"Lopez-Pascual","sequence":"first","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"Instituto de Investigaciones Sanitarias de Navarra IdiSNA","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Elurbide","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana","family":"Valbuena-Goiricelaya","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Ujue","family":"Latasa","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Anaya","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Adan-Villaescusa","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Castell\u00f3-Uribe","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz A.","family":"Mart\u00ednez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"Universidad de Guadalajara, Centro Universitarios de los Altos, Ciencias de la Salud","place":["Guadalajara, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iker","family":"Uriarte","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Arechederra","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"Instituto de Investigaciones Sanitarias de Navarra IdiSNA","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ciordia","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Centro Nacional de Biotecnolog\u00eda, CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"Corrales","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Centro Nacional de Biotecnolog\u00eda, CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Strnad","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen","place":["Aachen, Germany"]},{"name":"Department of Gastroenterology and Hepatology, Medical University Lausitz - Carl Thiem (MUL-CT)","place":["Cottbus, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Frankova","sequence":"additional","affiliation":[{"name":"Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sticova","sequence":"additional","affiliation":[{"name":"Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine","place":["Prague, Czechia"]},{"name":"Department of Pathology, 3rd Faculty of Medicine, Charles University and Kralovske Vinohrady University Hospital","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Fabian","sequence":"additional","affiliation":[{"name":"Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine","place":["Prague, Czechia"]},{"name":"Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University and Thomayer Hospital","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Colyn","sequence":"additional","affiliation":[{"name":"Max Plank Institute of Molecular Cell Biology and Genetics","place":["Dresden, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Inacio","sequence":"additional","affiliation":[{"name":"Max Plank Institute of Molecular Cell Biology and Genetics","place":["Dresden, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bayo","sequence":"additional","affiliation":[{"name":"Programa de Hepatolog\u00eda Experimental y Terapia G\u00e9nica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Huch","sequence":"additional","affiliation":[{"name":"Max Plank Institute of Molecular Cell Biology and Genetics","place":["Dresden, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Berasain","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maite G.","family":"Fern\u00e1ndez-Barrena","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"Instituto de Investigaciones Sanitarias de Navarra IdiSNA","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas A.","family":"Avila","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra","place":["Pamplona, Spain"]},{"name":"Instituto de Investigaciones Sanitarias de Navarra IdiSNA","place":["Pamplona, Spain"]},{"name":"CIBERehd, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.tibs.2025.06.005","article-title":"The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation","volume":"50","author":"Acu\u00f1a-Pilarte","year":"2025","journal-title":"Trends biochem. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1007\/S12072-019-09954-3","article-title":"Prognostic subclass of intrahepatic cholangiocarcinoma by integrative molecular-clinical analysis and potential targeted approach","volume":"13","author":"Ahn","year":"2019","journal-title":"Hepatol. Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/S41388-023-02646-1","article-title":"Combinatorial targeting of immune checkpoints and epigenetic regulators for hepatocellular carcinoma therapy","volume":"42","author":"Akce","year":"2023","journal-title":"Oncogene"},{"key":"B4","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12935-021-02425-6","article-title":"PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment","volume":"22","author":"Alberto-Aguilar","year":"2022","journal-title":"Cancer Cell. Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","article-title":"Comprehensive and integrative genomic characterization of hepatocellular carcinoma","volume":"169","author":"Ally","year":"2017","journal-title":"Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/J.JHEP.2023.03.010","article-title":"EASL-ILCA clinical practice guidelines on the management of intrahepatic cholangiocarcinoma","volume":"79","author":"Alvaro","year":"2023","journal-title":"J. Hepatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq-A python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1053\/J.GASTRO.2011.12.005","article-title":"Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors","volume":"142","author":"Andersen","year":"2012","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1158\/2326-6066.CIR-21-1101","article-title":"Molecular subgroups of intrahepatic cholangiocarcinoma discovered by single-cell RNA sequencing-assisted multiomics analysis","volume":"10","author":"Bao","year":"2022","journal-title":"Cancer Immunol. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/hep.30168","article-title":"Dual targeting of histone methyltransferase G9a and DNA\u2010Methyltransferase 1 for the treatment of experimental hepatocellular carcinoma","volume":"69","author":"B\u00e1rcena\u2010Varela","year":"2019","journal-title":"Hepatology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1021\/PR201223P","article-title":"Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression","volume":"11","author":"Barr","year":"2012","journal-title":"J. Proteome Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1056\/NEJMra1805035","article-title":"Epigenetic therapies for cancer","volume":"383","author":"Bates","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/S13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"171","author":"Becht","year":"2016","journal-title":"Genome Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/S41586-019-1103-9","article-title":"Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens","volume":"568","author":"Behan","year":"2019","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ejphar.2018.08.021","article-title":"Epigenetic tools (the writers, the readers and the erasers) and their implications in cancer therapy","volume":"837","author":"Biswas","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"768996","DOI":"10.3389\/fgene.2021.768996","article-title":"Metabolic fuel for epigenetic: nuclear production meets local consumption","volume":"12","author":"Boon","year":"2021","journal-title":"Front. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1038\/s42255-020-00285-4","article-title":"Nuclear metabolism and the regulation of the epigenome","volume":"2","author":"Boon","year":"2020","journal-title":"Nat. Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"Brindley","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1038\/nm.4438","article-title":"Human primary liver cancer\u2013derived organoid cultures for disease modeling and drug screening","volume":"23","author":"Broutier","year":"2017","journal-title":"Nat. Med."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2025-336317","article-title":"Epigenetic therapies in hepatocellular carcinoma: emerging clinical tools and applications","author":"Bueloni","year":"2025","journal-title":"Gut"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1111\/cns.14191","article-title":"G9a promotes immune suppression by targeting the Fbxw7\/Notch pathway in glioma stem cells","volume":"29","author":"Cao","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1158\/2159-8290.CD-18-0567","article-title":"Acetyl-CoA metabolism supports multistep pancreatic tumorigenesis","volume":"9","author":"Carrer","year":"2019","journal-title":"Cancer Discov."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/S13105-025-01095-6","article-title":"Expression landscape of epigenetic genes in human hepatocellular carcinoma","volume":"2025","author":"Castell\u00f3-Uribe","year":"2025","journal-title":"J. Physiol. Biochem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/J.CCELL.2017.05.009","article-title":"Common molecular subtypes among Asian hepatocellular carcinoma and cholangiocarcinoma","volume":"32","author":"Chaisaingmongkol","year":"2017","journal-title":"Cancer Cell."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0230-6","article-title":"The cancer driver genes IDH1\/2, JARID1C\/KDM5C, and UTX\/KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism","volume":"51","author":"Chang","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"gkae1210","DOI":"10.1093\/nar\/gkae1210","article-title":"Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence","volume":"53","author":"Chang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41419-017-0090-8","article-title":"Hepatic SMARCA4 predicts HCC recurrence and promotes tumour cell proliferation by regulating SMAD6 expression","volume":"9","author":"Chen","year":"2018","journal-title":"Cell. Death Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"478","DOI":"10.21037\/HBSN-21-424","article-title":"Epigenome-wide development and validation of a prognostic methylation score in intrahepatic cholangiocarcinoma based on machine learning strategies","volume":"12","author":"Chen","year":"2023","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1186\/s13046-024-03186-6","article-title":"STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A","volume":"43","author":"Chen","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s13046-022-02394-2","article-title":"The hippo pathway effector TAZ induces intrahepatic cholangiocarcinoma in mice and is ubiquitously activated in the human disease","volume":"41","author":"Cigliano","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"125988","DOI":"10.1016\/j.talanta.2024.125988","article-title":"Refinement of paramagnetic bead-based digestion protocol for automatic sample preparation using an artificial neural network","volume":"274","author":"Ciordia","year":"2024","journal-title":"Talanta"},{"key":"B33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.20517\/2395-5079.2021.77","article-title":"Epigenetics in hepatoblastoma","volume":"7","author":"Claveria-Cabello","year":"2021","journal-title":"Hepatoma Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/J.JHEP.2023.05.031","article-title":"Identification and experimental validation of druggable epigenetic targets in hepatoblastoma","volume":"79","author":"Claver\u00eda-Cabello","year":"2023","journal-title":"J. Hepatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1002\/hep.31642","article-title":"Dual targeting of G9a and DNA Methyltransferase-1 for the treatment of experimental cholangiocarcinoma","volume":"73","author":"Colyn","year":"2021","journal-title":"Hepatology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13046-022-02386-2","article-title":"New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming","volume":"41","author":"Colyn","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"101949","DOI":"10.1016\/j.bbrep.2025.101949","article-title":"Single-cell RNAseq reveals adverse metabolic transcriptional program in intrahepatic cholangiocarcinoma malignant cells","volume":"41","author":"Desterke","year":"2025","journal-title":"Biochem. Biophys. Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/J.JHEP.2023.10.041","article-title":"Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma","volume":"80","author":"DiPeri","year":"2023","journal-title":"J. Hepatol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-Seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/J.CCELL.2021.12.006","article-title":"Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma","volume":"40","author":"Dong","year":"2022","journal-title":"Cancer Cell."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1186\/S12967-025-07272-X","article-title":"Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy","volume":"23","author":"Dong","year":"2025","journal-title":"J. Transl. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"104657","DOI":"10.1016\/J.EBIOM.2023.104657","article-title":"DNA methylation-based classifier differentiates intrahepatic pancreato-biliary tumours","volume":"93","author":"Dragomir","year":"2023","journal-title":"EBioMedicine"},{"key":"B43","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrm4043","article-title":"DNA methylation pathways and their crosstalk with histone methylation","volume":"16","author":"Du","year":"2015","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/J.CMET.2016.08.009","article-title":"One-carbon metabolism in health and disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell. Metab."},{"key":"B45","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1136\/gutjnl-2024-332998","article-title":"Identification of PRMT5 as a therapeutic target in cholangiocarcinoma","volume":"74","author":"Elurbide","year":"2025","journal-title":"Gut"},{"key":"B46","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.canlet.2020.01.021","article-title":"Writers, readers and erasers of RNA modifications in cancer","volume":"474","author":"Esteve-Puig","year":"2020","journal-title":"Cancer Lett."},{"key":"B47","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.molcel.2016.05.029","article-title":"Interplay between metabolism and epigenetics: a nuclear adaptation to environmental changes","volume":"62","author":"Etchegaray","year":"2016","journal-title":"Mol. Cell."},{"key":"B48","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/S13148-022-01419-Z","article-title":"Drugging the epigenome in the age of precision medicine","volume":"15","author":"Feehley","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"B49","doi-asserted-by":"publisher","first-page":"100167","DOI":"10.1016\/j.jhepr.2020.100167","article-title":"Epigenetics in hepatocellular carcinoma development and therapy: the tip of the iceberg","volume":"2","author":"Fern\u00e1ndez-Barrena","year":"2020","journal-title":"JHEP Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"101980","DOI":"10.1016\/j.smim.2025.101980","article-title":"Epigenetic mechanisms in HCC immune landscape: therapeutic implications","volume":"79","author":"Fernandez-Barrena","year":"2025","journal-title":"Semin. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"S277","DOI":"10.21037\/atm.2019.11.140","article-title":"The many metabolic sources of acetyl-CoA to support histone acetylation and influence cancer progression","volume":"7","author":"Feron","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41586-019-1437-3","article-title":"Dietary methionine influences therapy in mouse cancer models and alters human metabolism","volume":"572","author":"Gao","year":"2019","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1136\/GUTJNL-2025-337579","article-title":"Molecular and cellular consequences of tumour-autonomous IL-6 signalling in intrahepatic cholangiocarcinoma","author":"Gehl","year":"2026","journal-title":"Gut"},{"key":"B54","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s12915-025-02423-4","article-title":"TCA-Cycle metabolites in the nucleus: drivers of chromatin and epigenetic control","volume":"23","author":"Ghisletti","year":"2025","journal-title":"BMC Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1136\/GUTJNL-2020-322983","article-title":"Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis","volume":"71","author":"Goeppert","year":"2022","journal-title":"Gut"},{"key":"B56","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41568-022-00543-5","article-title":"Acetyl-CoA metabolism in cancer","volume":"23","author":"Guertin","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"B57","doi-asserted-by":"publisher","first-page":"75441","DOI":"10.18632\/oncotarget.12254","article-title":"TACC3 overexpression in cholangiocarcinoma correlates with poor prognosis and is a potential anti-cancer molecular drug target for HDAC inhibitors","volume":"7","author":"He","year":"2016","journal-title":"Oncotarget"},{"key":"B58","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/S12859-015-0611-3","article-title":"InteractiVenn: a web-based tool for the analysis of sets through venn diagrams","volume":"161","author":"Heberle","year":"2015","journal-title":"BMC Bioinforma."},{"key":"B59","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s13105-023-00976-y","article-title":"Comprehensive analysis of epigenetic and epitranscriptomic genes\u2019 expression in human NAFLD","volume":"79","author":"Herranz","year":"2023","journal-title":"J. Physiol. Biochem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"eaaz0356","DOI":"10.1126\/SCIADV.AAZ0356","article-title":"PHF20L1 as a H3K27me2 reader coordinates with transcriptional repressors to promote breast tumorigenesis","volume":"6","author":"Hou","year":"2020","journal-title":"Sci. Adv."},{"key":"B61","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1152\/PHYSIOLGENOMICS.00040.2001","article-title":"A compendium of gene expression in normal human tissues","volume":"7","author":"Hsiao","year":"2001","journal-title":"Physiol. Genomics"},{"key":"B62","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1053\/J.GASTRO.2022.05.007","article-title":"NOTCH-YAP1\/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma","volume":"163","author":"Hu","year":"2022","journal-title":"Gastroenterology"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.2217\/EPI-2022-0320","article-title":"Combining EZH2 inhibitors with other therapies for solid tumors: more choices for better effects","volume":"14","author":"Huang","year":"2022","journal-title":"Epigenomics"},{"key":"B64","doi-asserted-by":"publisher","first-page":"793428","DOI":"10.3389\/fcell.2021.793428","article-title":"Interplay among metabolism, epigenetic modifications, and gene expression in cancer","volume":"9","author":"Huo","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/S41571-023-00770-1","article-title":"Cholangiocarcinoma - novel biological insights and therapeutic strategies","volume":"20","author":"Ilyas","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1038\/s12276-020-00539-x","article-title":"Histone acylation marks respond to metabolic perturbations and enable cellular adaptation","volume":"5212","author":"Jo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1002\/HEP.31092","article-title":"Identification of four immune subtypes characterized by distinct composition and functions of tumor microenvironment in intrahepatic cholangiocarcinoma","volume":"72","author":"Job","year":"2020","journal-title":"Hepatology"},{"key":"B68","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"B69","doi-asserted-by":"publisher","first-page":"10921","DOI":"10.1038\/s41598-017-11094-3","article-title":"CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the hippo pathway","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1158\/2159-8290.CD-17-0368","article-title":"Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma","volume":"7","author":"Jusakul","year":"2017","journal-title":"Cancer Discov."},{"key":"B71","doi-asserted-by":"publisher","first-page":"D199","DOI":"10.1093\/nar\/gkt1076","article-title":"Data, information, knowledge and principle: back to metabolism in KEGG","volume":"42","author":"Kanehisa","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1089\/cmb.2017.0096","article-title":"CutPrimers: a new tool for accurate cutting of primers from reads of targeted next generation sequencing","volume":"24","author":"Kechin","year":"2017","journal-title":"J. Comput. Biol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ircmb.2024.09.002","article-title":"Revisiting epigenetic regulation in cancer: evolving trends and translational implications","volume":"390","author":"Khan","year":"2025","journal-title":"Int. Rev. Cell. Mol. Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/NATURE20132","article-title":"LKB1 loss links serine metabolism to DNA methylation and tumorigenesis","volume":"539","author":"Kottakis","year":"2016","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1128\/MCB.00444-09","article-title":"Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth","volume":"30","author":"Krieg","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s13059-023-03020-w","article-title":"Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal","volume":"24","author":"Krill-Burger","year":"2023","journal-title":"Genome Biol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"11643","DOI":"10.1093\/nar\/gkx747","article-title":"Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia","volume":"45","author":"Lee","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The SVA package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"B79","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41580-018-0029-7","article-title":"Regulation of chromatin and gene expression by metabolic enzymes and metabolites","volume":"19","author":"Li","year":"2018","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13148-021-01016-6","article-title":"Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4\/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner","volume":"13","author":"Li","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"B81","doi-asserted-by":"publisher","first-page":"167276","DOI":"10.1016\/j.bbadis.2024.167276","article-title":"Single-cell analysis reveals hypoxia-induced immunosuppressive microenvironment in intrahepatic cholangiocarcinoma","volume":"1870","author":"Liang","year":"2024","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"B82","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/S13148-021-01100-X","article-title":"Leveraging epigenetics to enhance the efficacy of immunotherapy","volume":"13","author":"Licht","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1093\/bioinformatics\/bts340","article-title":"ChromoHub: a data hub for navigators of chromatin-mediated signalling","volume":"28","author":"Liu","year":"2012","journal-title":"Bioinformatics"},{"key":"B84","doi-asserted-by":"publisher","first-page":"101182","DOI":"10.1016\/j.jhepr.2024.101182","article-title":"Altered fatty acid metabolism rewires cholangiocarcinoma stemness features","volume":"6","author":"Lori","year":"2024","journal-title":"JHEP Rep."},{"key":"B85","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/nature10860","article-title":"IDH mutation impairs histone demethylation and results in a block to cell differentiation","volume":"2012","author":"Lu","year":"2012","journal-title":"Nat"},{"key":"B86","first-page":"5728","article-title":"BRD4 degrader ARV-825 produces long-lasting loss of BRD4 protein and exhibits potent efficacy against cholangiocarcinoma cells","volume":"11","author":"Lu","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"B87","doi-asserted-by":"publisher","first-page":"101417","DOI":"10.1016\/J.JCMGH.2024.101417","article-title":"Notch-driven cholangiocarcinogenesis involves the hippo pathway effector TAZ via METTL3-m6A-YTHDF1","volume":"19","author":"Ma","year":"2024","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1126\/science.adj3020","article-title":"Nutrient-driven histone code determines exhausted CD8+ T cell fates","volume":"80","author":"Ma","year":"2025","journal-title":"Science"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1136\/gutjnl-2022-327099","article-title":"Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions","volume":"71","author":"Macias","year":"2022","journal-title":"Gut"},{"key":"B90","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1055\/a-2207-9834","article-title":"Biliary tract cancer: molecular biology of precursor lesions","volume":"43","author":"Manzano-N\u00fa\u00f1ez","year":"2023","journal-title":"Semin. Liver Dis."},{"key":"B91","doi-asserted-by":"publisher","first-page":"D564","DOI":"10.1093\/nar\/gkac989","article-title":"EpiFactors 2022: expansion and enhancement of a curated database of human epigenetic factors and complexes","volume":"51","author":"Marakulina","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/j.bbadis.2017.06.005","article-title":"Chemoresistance and chemosensitization in cholangiocarcinoma","volume":"1864","author":"Marin","year":"2018","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"B93","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet.J."},{"key":"B94","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1136\/GUTJNL-2021-326514","article-title":"Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications","volume":"72","author":"Martin-Serrano","year":"2023","journal-title":"Gut"},{"key":"B95","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.jprot.2015.01.019","article-title":"Enhancing metabolomics research through data mining","volume":"127","author":"Mart\u00ednez-Arranz","year":"2015","journal-title":"J. Proteomics"},{"key":"B96","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cmet.2015.08.024","article-title":"Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism","volume":"22","author":"Mentch","year":"2015","journal-title":"Cell. Metab."},{"key":"B97","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jhep.2017.02.017","article-title":"SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma","volume":"67","author":"Merino-Azpitarte","year":"2017","journal-title":"J. Hepatol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1038\/ng.3984","article-title":"Computational correction of copy number effect improves specificity of CRISPR\u2013Cas9 essentiality screens in cancer cells","volume":"49","author":"Meyers","year":"2017","journal-title":"Nat. Genet."},{"key":"B99","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/S41231-023-00154-8","article-title":"Unraveling the complexity: understanding the deconvolutions of RNA-seq data","volume":"81","author":"Momeni","year":"2023","journal-title":"Transl. Med. Commun."},{"key":"B100","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.jhep.2020.03.008","article-title":"Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma","volume":"73","author":"Montal","year":"2020","journal-title":"J. Hepatol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1038\/S41588-020-00736-4","article-title":"Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation","volume":"52","author":"Morgan","year":"2020","journal-title":"Nat. Genet."},{"key":"B102","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1146\/ANNUREV-PATHMECHDIS-111523-023424","article-title":"Integration and intersection of cancer metabolism with epigenetic pathways in gliomas","volume":"21","author":"Natarajan","year":"2025","journal-title":"Annu. Rev. Pathol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13046-024-03268-5","article-title":"Targeting of the G9a, DNMT1 and UHRF1 epigenetic complex as an effective strategy against pancreatic ductal adenocarcinoma","volume":"44","author":"Oyon","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.bbadis.2017.06.014","article-title":"Epigenome dysregulation in cholangiocarcinoma","volume":"1864","author":"O\u2019Rourke","year":"2018","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"B105","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.trecan.2019.05.002","article-title":"Epigenome remodeling in cholangiocarcinoma","volume":"5","author":"O\u2019Rourke","year":"2019","journal-title":"Trends Cancer"},{"key":"B106","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1136\/gutjnl-2023-330748","article-title":"Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy","volume":"73","author":"O\u2019Rourke","year":"2023","journal-title":"Gut"},{"key":"B107","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1089\/ars.2017.7237","article-title":"Mammalian sulfur amino acid metabolism: a nexus between redox regulation, nutrition, epigenetics, and detoxification","volume":"29","author":"Pajares","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"B108","doi-asserted-by":"publisher","first-page":"102223","DOI":"10.1016\/j.clinre.2023.102223","article-title":"New epidemiologic trends in cholangiocarcinoma","volume":"47","author":"Pascale","year":"2023","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"762598","DOI":"10.3389\/fimmu.2021.762598","article-title":"A pan-cancer analysis of SMARCA4 alterations in human cancers","volume":"12","author":"Peng","year":"2021","journal-title":"Front. Immunol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/j.jhep.2020.12.031","article-title":"Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma","volume":"74","author":"Raggi","year":"2021","journal-title":"J. Hepatol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.jhep.2022.04.038","article-title":"Metabolic reprogramming in cholangiocarcinoma","volume":"77","author":"Raggi","year":"2022","journal-title":"J. Hepatol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1038\/NCB3629","article-title":"The impact of cellular metabolism on chromatin dynamics and epigenetics","volume":"19","author":"Reid","year":"2017","journal-title":"Nat. Cell. Biol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"201907022","DOI":"10.1083\/jcb.201907022","article-title":"The complexity of the serine glycine one-carbon pathway in cancer","volume":"219","author":"Reina-Campos","year":"2019","journal-title":"J. Cell. Biol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2009","journal-title":"Bioinformatics"},{"key":"B115","doi-asserted-by":"publisher","first-page":"5330","DOI":"10.1038\/s41467-018-07232-8","article-title":"Pan-cancer analysis of transcriptional metabolic dysregulation using the cancer genome atlas","volume":"9","author":"Rosario","year":"2018","journal-title":"Nat. Commun."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1136\/gutjnl-2021-324109","article-title":"GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity","volume":"71","author":"Ruffolo","year":"2022","journal-title":"Gut"},{"key":"B117","first-page":"13246","article-title":"Cholangiocarcinoma: the role of genetic and epigenetic factors; current and prospective treatment with checkpoint inhibitors and immunotherapy","volume":"13","author":"Sarantis","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"B118","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41575-019-0217-8","article-title":"Metabolic rearrangements in primary liver cancers: cause and consequences","volume":"16","author":"Satriano","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: a bridge between the gene expression omnibus (GEO) and BioConductor","volume":"23","author":"Sean","year":"2007","journal-title":"Bioinformatics"},{"key":"B120","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1053\/j.gastro.2013.01.001","article-title":"Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes","volume":"144","author":"Sia","year":"2013","journal-title":"Gastroenterology"},{"key":"B121","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s10555-022-10071-1","article-title":"Hypoxia signaling in hepatocellular carcinoma: challenges and therapeutic opportunities","volume":"42","author":"Sin","year":"2023","journal-title":"Cancer Metastasis Rev."},{"key":"B122","doi-asserted-by":"publisher","first-page":"S68","DOI":"10.1016\/j.cgh.2009.08.023","article-title":"Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms","volume":"7","author":"Sirica","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/S12094-025-03995-X","article-title":"Clinical progress and functional modalities of HDAC inhibitor-based combination therapies in cancer treatment","volume":"28","author":"Talom","year":"2025","journal-title":"Clin. Transl. Oncol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","article-title":"Biliary tract cancer","volume":"397","author":"Valle","year":"2021","journal-title":"Lancet London, Engl."},{"key":"B125","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.it.2020.06.002","article-title":"The contribution of epigenetics to cancer immunotherapy","volume":"41","author":"Villanueva","year":"2020","journal-title":"Trends Immunol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"D1063","DOI":"10.1093\/nar\/gks1262","article-title":"The proteomics identifications (PRIDE) database and associated tools: status in 2013","volume":"41","author":"Vizca\u00edno","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B127","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/S40880-018-0302-3","article-title":"Metabolic recoding of epigenetics in cancer","volume":"38","author":"Wang","year":"2018","journal-title":"Cancer Commun."},{"key":"B128","doi-asserted-by":"publisher","first-page":"152451","DOI":"10.1016\/j.prp.2019.152451","article-title":"Overexpression of polycomb repressive complex 2 key components EZH2\/SUZ12\/EED as an unfavorable prognostic marker in cholangiocarcinoma","volume":"215","author":"Wasenang","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"B129","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1126\/science.1164097","article-title":"ATP-Citrate lyase links cellular metabolism to histone acetylation","volume":"324","author":"Wellen","year":"2009","journal-title":"Sci."},{"key":"B130","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1158\/2159-8290.CD-21-1077","article-title":"Mutant IDH inhibits IFN\u03b3\u2013TET2 signaling to promote immunoevasion and tumor maintenance in cholangiocarcinoma","volume":"12","author":"Wu","year":"2022","journal-title":"Cancer Discov."},{"key":"B131","doi-asserted-by":"publisher","first-page":"e1502","DOI":"10.1002\/ctm2.1502","article-title":"Targeting polycomb repressor complex 2\u2010mediated bivalent promoter epigenetic silencing of secreted frizzled\u2010related protein 1 inhibits cholangiocarcinoma progression","volume":"13","author":"Wu","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"B132","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.clinre.2013.11.004","article-title":"Si-DNMT1 restore tumor suppressor genes expression through the reversal of DNA hypermethylation in cholangiocarcinoma","volume":"38","author":"Xiang","year":"2014","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"e2400413","DOI":"10.1002\/adbi.202400413","article-title":"CBX3 downregulates HLTF to activate PI3K\/AKT signaling promoting cholangiocarcinoma","volume":"9","author":"Xie","year":"2025","journal-title":"Adv. Biol."},{"key":"B134","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13046-024-03070-3","article-title":"Unveiling the role of HP1\u03b1-HDAC1-STAT1 axis as a therapeutic target for HP1\u03b1-positive intrahepatic cholangiocarcinoma","volume":"43","author":"Xiong","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B135","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/s41419-022-04571-9","article-title":"Suppression of histone deacetylase 1 by JSL-1 attenuates the progression and metastasis of cholangiocarcinoma via the TPX2\/Snail axis","volume":"13","author":"Xu","year":"2022","journal-title":"Cell. Death Dis."},{"key":"B136","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1172\/JCI67228","article-title":"Oncometabolites: linking altered metabolism with cancer","volume":"123","author":"Yang","year":"2013","journal-title":"J. Clin. Invest."},{"key":"B137","doi-asserted-by":"publisher","first-page":"e2856","DOI":"10.1038\/cddis.2016.457","article-title":"Histone deacetylase 3 overexpression in human cholangiocarcinoma and promotion of cell growth via apoptosis inhibition","volume":"8","author":"Yin","year":"2017","journal-title":"Cell. Death Dis."},{"key":"B138","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/j.molcel.2019.06.039","article-title":"One-carbon metabolism supports S-Adenosylmethionine and histone methylation to drive inflammatory macrophages","volume":"75","author":"Yu","year":"2019","journal-title":"Mol. Cell."},{"key":"B139","first-page":"1013","article-title":"Primary cholangiocellular carcinoma cell lines","volume":"2","author":"Zach","year":"2015","journal-title":"J. Stem Cell. Res. Transpl."},{"key":"B140","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/S12935-019-1080-Y","article-title":"Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma","volume":"19","author":"Zhang","year":"2019","journal-title":"Cancer Cell. Int."},{"key":"B141","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1016\/j.ajpath.2022.08.008","article-title":"EZH2 promotes cholangiocarcinoma development and progression through histone methylation and microRNA-Mediated down-regulation of tumor suppressor genes","volume":"192","author":"Zhang","year":"2022","journal-title":"Am. J. Pathol."},{"key":"B142","doi-asserted-by":"publisher","first-page":"1028404","DOI":"10.3389\/fimmu.2023.1028404","article-title":"Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Immunol."},{"key":"B143","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/cr.2009.61","article-title":"RLEdb: a database of rate-limiting enzymes and their regulation in human, rat, mouse, yeast and E. coli","volume":"19","author":"Zhao","year":"2009","journal-title":"Cell. Res."},{"key":"B144","doi-asserted-by":"publisher","first-page":"e151","DOI":"10.1111\/LIV.12503;WGROUP:STRING:PUBLICATION","article-title":"CHD5 a tumour suppressor is epigenetically silenced in hepatocellular carcinoma","volume":"34","author":"Zhao","year":"2014","journal-title":"Liver Int."},{"key":"B145","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/s41568-021-00357-x","article-title":"The language of chromatin modification in human cancers","volume":"21","author":"Zhao","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"B146","doi-asserted-by":"publisher","first-page":"115290","DOI":"10.1016\/j.biopha.2023.115290","article-title":"The roles of epigenetic regulation in cholangiocarcinogenesis","volume":"166","author":"Zhong","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B147","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1186\/s12967-024-05238-z","article-title":"Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma","volume":"22","author":"Zhong","year":"2024","journal-title":"J. Transl. Med."},{"key":"B148","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/hep.31780","article-title":"Brahma-related gene 1 inhibition prevents liver fibrosis and cholangiocarcinoma by attenuating progenitor expansion","volume":"74","author":"Zhou","year":"2021","journal-title":"Hepatology"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1765945\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:30:01Z","timestamp":1780547401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1765945\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":148,"alternative-id":["10.3389\/fcell.2026.1765945"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1765945","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]},"article-number":"1765945"}}