{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:14:05Z","timestamp":1788146045768,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2022\/45\/N\/NZ7\/01780"],"award-info":[{"award-number":["2022\/45\/N\/NZ7\/01780"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2022\/45\/N\/NZ7\/01780"],"award-info":[{"award-number":["2022\/45\/N\/NZ7\/01780"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors, which are usually treated with surgery and radiotherapy, while chemotherapy (e.g., cisplatin), anti-EGFR, or immune checkpoint inhibitors are used to treat locoregionally advanced and recurrent cases. However, survival outcomes are still unsatisfactory, and novel augmenting treatments are required. Recently, histone lysine demethylases (KDMs) emerged as promising anti-cancer targets. In order to further characterize KDM4\u20136 as pharmacological targets in HNSCC, we evaluated changes in KDM4\/5\/6 expression in HNSCC patients, and we experimentally assessed the biological effects of inhibitors of KDM4\/5\/6 in HNSCC cell lines. Methods: We used online tools (TIMER, GEPIA3, UALCAN) to analyze TCGA data from HNSCC patients. Then, we used resazurin assay to assess the effect of ML324, GSK-J4, and JIB-04 (the inhibitors of KDM4, KDM6, and KDM4\u20136, respectively) on cell viability in two-dimensional (2D) and three-dimensional (3D) culture of FaDu, SCC-152, and Detroit-562 cells. The potential for cisplatin sensitization was also assessed. Gene\/protein expression was evaluated by qPCR and antibody array. Results: We found that the majority of the analyzed KDMs were overexpressed in HNSCC, except KDM4C, KDM5D, and KDM6A. All three studied inhibitors significantly reduced cell viability in 2D and 3D cell cultures. Moreover, the pre-treatment of cells with KDM inhibitors showed moderate potential for cisplatin sensitization. In addition, the chemicals significantly reduced the expression of pluripotency markers, especially SOX2. Conclusions: In conclusion, KDM4\u20136 inhibitors significantly affected HNSCC cell growth, and exerted the potential for epigenetic priming in combination with cisplatin.<\/jats:p>","DOI":"10.3390\/genes17091047","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Inhibition of Histone Lysine Demethylases Affects Head and Neck Cancer Cell Growth and Response to Cisplatin"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-5327","authenticated-orcid":false,"given":"Dawid","family":"Dorna","sequence":"first","affiliation":[{"name":"Poznan University of Medical Sciences, Doctoral School, 60-812 Pozna\u0144, Poland"},{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6607-7436","authenticated-orcid":false,"given":"Robert","family":"Kleszcz","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7275-0298","authenticated-orcid":false,"given":"Violetta","family":"Krajka-Ku\u017aniak","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-7549","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Paluszczak","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sun, H., Yu, M., An, Z., Liang, F., Sun, B., Liu, Y., and Zhang, S. (2025). Global Burden of Head and Neck Cancer: Epidemiological Transitions, Inequities, and Projections to 2050. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1665019"},{"key":"ref_2","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e70467","DOI":"10.1002\/mco2.70467","article-title":"Incidence, Risk Factors, and Epidemiological Trends of Head and Neck Cancer: A Global Analysis","volume":"6","author":"Huang","year":"2025","journal-title":"MedComm"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Barsouk, A., Aluru, J.S., Rawla, P., Saginala, K., and Barsouk, A. (2023). Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med. Sci., 11.","DOI":"10.3390\/medsci11020042"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Huang, Q., Li, F., Ji, M., Lin, L., and Hu, C. (2023). Evaluating the Prognostic Significance of P53 and TP53 Mutations in HPV-Negative Hypopharyngeal Carcinoma Patients: A 5-Year Follow-up Retrospective Study. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10775-9"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"de Oliveira, L.Q.R., Farshadi, F., Mlynarek, A., Mascarella, M.A., Hier, M., Coletta, R.D., and Wurzba, S.D.S. (2026). P53 Positivity Predicts Poor Survival in Oropharyngeal Squamous Cell Carcinoma Dependent on HPV Status. Cancers, 18.","DOI":"10.3390\/cancers18101660"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.otc.2017.03.013","article-title":"Systemic Treatment for Squamous Cell Carcinoma of the Head and Neck","volume":"50","author":"Shetty","year":"2017","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101426","DOI":"10.1016\/j.tranon.2022.101426","article-title":"Therapeutic Approaches for the Treatment of Head and Neck Squamous Cell Carcinoma\u2013An Update on Clinical Trials","volume":"21","author":"Goel","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/17501911.2024.2430169","article-title":"Cancer Epigenetic Therapy: Recent Advances, Challenges, and Emerging Opportunities","volume":"17","author":"Vatapalli","year":"2025","journal-title":"Epigenomics"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gupta, P. (2025). Epigenetic Alterations in Cancer: The Therapeutic Potential of Epigenetic Drugs in Cancer Therapy. Drugs Drug Candidates, 4.","DOI":"10.3390\/ddc4020015"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10555-025-10253-7","article-title":"Epigenetic Drugs in Cancer Therapy","volume":"44","author":"Suraweera","year":"2025","journal-title":"Cancer Metastasis Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100192","DOI":"10.1016\/j.mocell.2025.100192","article-title":"Current Advances and Future Directions in Targeting Histone Demethylases for Cancer Therapy","volume":"48","author":"Shin","year":"2025","journal-title":"Mol. Cells"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dorna, D., and Paluszczak, J. (2022). The Emerging Significance of Histone Lysine Demethylases as Prognostic Markers and Therapeutic Targets in Head and Neck Cancers. Cells, 11.","DOI":"10.3390\/cells11061023"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Paluszczak, J., and Kleszcz, R. (2025). The Targeted Inhibition of Histone Lysine Demethylases as a Novel Promising Anti-Cancer Therapeutic Strategy\u2014An Update on Recent Evidence. Cancers, 17.","DOI":"10.3390\/cancers17172798"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10016","DOI":"10.7150\/thno.47081","article-title":"Targeted Inhibition of KDM6 Histone Demethylases Eradicates Tumor-Initiating Cells via Enhancer Reprogramming in Colorectal Cancer","volume":"10","author":"Zhang","year":"2020","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Michelutti, L., Tel, A., Zeppieri, M., Martinazzo, C., Robiony, M., Gagliano, C., D\u2019Esposito, F., Capobianco, M., and Khouyyi, M. (2025). Biological and Therapeutic Roles of Stem Cells in Head and Neck Carcinoma: Implications for Maxillofacial Surgery. Diseases, 13.","DOI":"10.3390\/diseases13120381"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1158\/0008-5472.CAN-16-0834","article-title":"Transcriptional Selectivity of Epigenetic Therapy in Cancer","volume":"77","author":"Sato","year":"2017","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/15384047.2021.2020060","article-title":"Inhibitors of Jumonji C Domain-Containing Histone Lysine Demethylases Overcome Cisplatin and Paclitaxel Resistance in Non-Small Cell Lung Cancer through APC\/Cdh1-Dependent Degradation of CtIP and PAF15","volume":"23","author":"Duan","year":"2022","journal-title":"Cancer Biol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13148-018-0605-x","article-title":"Elevated H3K27me3 Levels Sensitize Osteosarcoma to Cisplatin","volume":"11","author":"He","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/iub.2110","article-title":"Antiproliferative Effect of the Histone Demethylase Inhibitor GSK-J4 in Chondrosarcomas","volume":"71","author":"Lhuissier","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dorna, D., Kleszcz, R., and Paluszczak, J. (2024). Triple Combinations of Histone Lysine Demethylase Inhibitors with PARP1 Inhibitor\u2013Olaparib and Cisplatin Lead to Enhanced Cytotoxic Effects in Head and Neck Cancer Cells. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061359"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10120-019-01010-1","article-title":"Epigenetic Priming Sensitizes Gastric Cancer Cells to Irinotecan and Cisplatin by Restoring Multiple Pathways","volume":"23","author":"Moro","year":"2020","journal-title":"Gastric Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.18632\/oncotarget.2695","article-title":"Evaluation of Azacitidine and Entinostat as Sensitization Agents to Cytotoxic Chemotherapy in Preclinical Models of Non-Small Cell Lung Cancer","volume":"6","author":"Vendetti","year":"2014","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"W534","DOI":"10.1093\/nar\/gkaf388","article-title":"TIMER3: An Enhanced Resource for Tumor Immune Analysis","volume":"53","author":"Cui","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for Analysis of Tumor-Infiltrating Immune Cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W283","DOI":"10.1093\/nar\/gkaf423","article-title":"GEPIA3: Enhanced Drug Sensitivity and Interaction Network Analysis for Cancer Research","volume":"53","author":"Kang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses","volume":"19","author":"Chandrashekar","year":"2017","journal-title":"Neoplasia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","article-title":"UALCAN: An Update to the Integrated Cancer Data Analysis Platform","volume":"25","author":"Chandrashekar","year":"2022","journal-title":"Neoplasia"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kleszcz, R., Fr\u0105ckowiak, M., Dorna, D., and Paluszczak, J. (2023). Combinations of PRI-724 Wnt\/\u03b2-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310448"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115042","DOI":"10.1016\/j.yexcr.2026.115042","article-title":"The Combinations of Histone Lysine Demethylase Inhibitors with Panobinostat Exert Enhanced Effects against Head and Neck Cancer Cells","volume":"460","author":"Dorna","year":"2026","journal-title":"Exp. Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein\u2013Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"470283","DOI":"10.1155\/2015\/470283","article-title":"The Effect of Primary Cancer Cell Culture Models on the Results of Drug Chemosensitivity Assays: The Application of Perfusion Microbioreactor System as Cell Culture Vessel","volume":"2015","author":"Hsieh","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gori\u010dan, L., Gole, B., and Poto\u010dnik, U. (2020). Head and Neck Cancer Stem Cell-Enriched Spheroid Model for Anticancer Compound Screening. Cells, 9.","DOI":"10.3390\/cells9071707"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13417","DOI":"10.1007\/s00432-023-05136-9","article-title":"Targeting Cancer Stem Cells as a Strategy for Reducing Chemotherapy Resistance in Head and Neck Cancers","volume":"149","author":"Dorna","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xu, X., Tian, X., Song, L., Xie, J., Liao, J.C., Meeks, J.J., Wu, X.-R., Gin, G.E., Wang, B., and Uchio, E. (2023). Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation. Biomolecules, 13.","DOI":"10.3390\/biom13030521"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1158\/1940-6207.CAPR-20-0186","article-title":"Evidence That EZH2 Deregulation Is an Actionable Therapeutic Target for Prevention of Prostate Cancer","volume":"13","author":"Burkhart","year":"2020","journal-title":"Cancer Prev. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1158\/1541-7786.MCR-21-0310","article-title":"Inhibition of LSD1 Attenuates Oral Cancer Development and Promotes Therapeutic Efficacy of Immune Checkpoint Blockade and YAP\/TAZ Inhibition","volume":"20","author":"Alhousami","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1101\/gad.351444.123","article-title":"Epigenetic Modulators Provide a Path to Understanding Disease and Therapeutic Opportunity","volume":"38","author":"Honer","year":"2024","journal-title":"Genes Dev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Adamczuk, K., Miziak, P., Adamczuk, G., Baran, M., Nees, M., and Stepulak, A. (2026). Overcoming Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma (HNSCC): The Role of Histone Methyltransferase and Demethylase Inhibitors. Cancers, 18.","DOI":"10.20944\/preprints202605.0261.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.cell.2025.02.023","article-title":"20 Years of Histone Lysine Demethylases: From Discovery to the Clinic and Beyond","volume":"188","author":"Gray","year":"2025","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112402","DOI":"10.1016\/j.cellsig.2026.112402","article-title":"KDM5D Epigenetically Represses FERD3L to Inhibit Tumor Growth in Male Colorectal Cancer","volume":"142","author":"Yu","year":"2026","journal-title":"Cell. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e2402022121","DOI":"10.1073\/pnas.2402022121","article-title":"KDM5D Histone Demethylase Mediates P38\u03b1 Inactivation via Its Enzymatic Activity to Inhibit Cancer Progression","volume":"121","author":"Chen","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/hed.70070","article-title":"Loss of the Y Chromosome in Oral Potentially Premalignant Disorders Predicts Malignant Progression: An Integrative Cross-Species Multi-Cohort Bioinformatic Study","volume":"48","author":"Han","year":"2026","journal-title":"Head Neck"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105961","DOI":"10.1016\/j.ejps.2021.105961","article-title":"The Inhibitors of KDM4 and KDM6 Histone Lysine Demethylases Enhance the Anti-Growth Effects of Erlotinib and HS-173 in Head and Neck Cancer Cells","volume":"166","author":"Kleszcz","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3390\/ddc3020024","article-title":"Two-Dimensional and Spheroid-Based Three-Dimensional Cell Culture Systems: Implications for Drug Discovery in Cancer","volume":"3","author":"Garnique","year":"2024","journal-title":"Drugs Drug Candidates"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41419-023-06024-3","article-title":"Carcinogenesis Promotion in Oral Squamous Cell Carcinoma: KDM4A Complex-Mediated Gene Transcriptional Suppression by LEF1","volume":"14","author":"Hou","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s00018-025-05693-x","article-title":"KDM4C Works in Concert with GATA1 to Regulate Heme Metabolism in Head and Neck Squamous Cell Carcinoma","volume":"82","author":"Wu","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.3892\/or.2015.3849","article-title":"PLU-1\/JARID1B Overexpression Predicts Proliferation Properties in Head and Neck Squamous Cell Carcinoma","volume":"33","author":"Cui","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"339","DOI":"10.21873\/cgp.20324","article-title":"Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts","volume":"19","author":"Sanchez","year":"2022","journal-title":"Cancer Genom. Proteom."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dalpatraj, N., Naik, A., and Thakur, N. (2023). Combination Treatment of a Phytochemical and a Histone Demethylase Inhibitor\u2014A Novel Approach towards Targeting TGF\u03b2-Induced EMT, Invasion, and Migration in Prostate Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031860"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13148-024-01665-3","article-title":"Targeting Histone Demethylases JMJD3 and UTX: Selenium as a Potential Therapeutic Agent for Cervical Cancer","volume":"16","author":"Chen","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.7150\/thno.53347","article-title":"KDM6B-Mediated Histone Demethylation of LDHA Promotes Lung Metastasis of Osteosarcoma","volume":"11","author":"Jiang","year":"2021","journal-title":"Theranostics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1167\/iovs.65.2.34","article-title":"Antitumoral Potential of the Histone Demethylase Inhibitor GSK-J4 in Retinoblastoma","volume":"65","author":"Zhang","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s12935-024-03504-0","article-title":"KDM4A Promotes Malignant Progression of Breast Cancer by Down-Regulating BMP9 Inducing Consequent Enhancement of Glutamine Metabolism","volume":"24","author":"Chen","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lee, J., Kim, J.-S., Cho, H.-I., Jo, S.-R., and Jang, Y.-K. (2022). JIB-04, a Pan-Inhibitor of Histone Demethylases, Targets Histone-Lysine-Demethylase-Dependent AKT Pathway, Leading to Cell Cycle Arrest and Inhibition of Cancer Stem-Like Cell Properties in Hepatocellular Carcinoma Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147657"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"114350","DOI":"10.1016\/j.biopha.2023.114350","article-title":"Luteolin Directly Binds to KDM4C and Attenuates Ovarian Cancer Stemness via Epigenetic Suppression of PPP2CA\/YAP Axis","volume":"160","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1621054","DOI":"10.1155\/2019\/1621054","article-title":"GASC1 Promotes Stemness of Esophageal Squamous Cell Carcinoma via NOTCH1 Promoter Demethylation","volume":"2019","author":"Jia","year":"2019","journal-title":"J. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.canlet.2015.07.003","article-title":"Silencing JARID1B Suppresses Oncogenicity, Stemness and Increases Radiation Sensitivity in Human Oral Carcinoma","volume":"368","author":"Lin","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5538","DOI":"10.1158\/0008-5472.CAN-15-3377","article-title":"JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers","volume":"76","author":"Facompre","year":"2016","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8985","DOI":"10.18632\/oncotarget.23739","article-title":"Targeting JARID1B\u2019s Demethylase Activity Blocks a Subset of Its Functions in Oral Cancer","volume":"9","author":"Facompre","year":"2017","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Shait Mohammed, M.R., Zamzami, M., Choudhry, H., Ahmed, F., Ateeq, B., and Khan, M.I. (2022). The Histone H3K27me3 Demethylases KDM6A\/B Resist Anoikis and Transcriptionally Regulate Stemness-Related Genes. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.780176"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4607","DOI":"10.1172\/JCI138577","article-title":"Chemotherapy-Induced S100A10 Recruits KDM6A to Facilitate OCT4-Mediated Breast Cancer Stemness","volume":"130","author":"Lu","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wang, W.-P., Tzeng, T.-Y., Wang, J.-Y., Lee, D.-C., Lin, Y.-H., Wu, P.-C., Chen, Y.-P., Chiu, I.-M., and Chi, Y.-H. (2012). The EP300, KDM5A, KDM6A and KDM6B Chromatin Regulators Cooperate with KLF4 in the Transcriptional Activation of POU5F1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052556"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Griso, A.B., Acero-Riaguas, L., Castelo, B., Cebri\u00e1n-Carretero, J.L., and Sastre-Perona, A. (2022). Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas. Cells, 11.","DOI":"10.3390\/cells11030561"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41420-023-01418-w","article-title":"KDM4C Silencing Inhibits Cell Migration and Enhances Radiosensitivity by Inducing CXCL2 Transcription in Hepatocellular Carcinoma","volume":"9","author":"Zeng","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.2174\/0115665240281083241112053145","article-title":"KDM4A Silencing Reverses Cisplatin Resistance in Ovarian Cancer Cells by Reducing Mitophagy via SNCA Transcriptional Inactivation","volume":"25","author":"Xing","year":"2025","journal-title":"Curr. Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41418-024-01257-x","article-title":"Deubiquitinase USP7 Stabilizes KDM5B and Promotes Tumor Progression and Cisplatin Resistance in Nasopharyngeal Carcinoma through the ZBTB16\/TOP2A Axis","volume":"31","author":"Zhang","year":"2024","journal-title":"Cell Death Differ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1186\/s12964-024-01912-3","article-title":"Refractory Testicular Germ Cell Tumors Are Highly Sensitive to the Targeting of Polycomb Pathway Demethylases KDM6A and KDM6B","volume":"22","author":"Shokry","year":"2024","journal-title":"Cell Commun. Signal."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1047\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:23:14Z","timestamp":1788142994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":69,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091047"],"URL":"https:\/\/doi.org\/10.3390\/genes17091047","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]}}}