{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T21:11:59Z","timestamp":1774991519758,"version":"3.50.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Conventionally, KDM5C functions as a specific demethylase that targets histone H3 lysine 4 dimethyl and trimethyl modifications, crucial for gene expression. However, the role of KDM5C in multiple myeloma (MM) progression and bortezomib (BTZ) resistance has remained elusive. In this study, we found noncanonical functions of KDM5C in MM. Specifically, KDM5C binds to CBP and MYC, conferring BTZ resistance in MM through a demethylase-independent mechanism. Our investigations revealed that KDM5C is markedly upregulated in BTZ-resistant MM patients as well as those with relapsed MM. Significantly, the expression level of KDM5C exhibits an inverse correlation with the overall survival of MM patients. Moreover, KDM5C is indispensable for MM cell proliferation. Depletion of KDM5C augmented the sensitivity of MM cells to BTZ treatment both in vitro and in vivo. We found that KDM5C forms a novel complex with CBP and MYC via its PHD2 domain. This complex formation triggers lysine 27 acetylation in histone H3 (H3K27ac) and subsequent enrichment of H3K27ac on the PERK promoter. As a result, PERK transcription is activated, and Nrf2 phosphorylation is promoted, bolstering the unfolded protein response within the endoplasmic reticulum of MM cells. In contrast, the methylation status of histone H3 lysine 4 (H3K4me1\/3) on the PERK promoter remains unaltered, regardless of the complex state. Taken together, the findings of this study underscore the key role of KDM5C as a driving force behind MM progression and BTZ resistance, indicating that KDM5C represents a novel and promising therapeutic target for the treatment of BTZ-resistant MM.<\/jats:p>","DOI":"10.1038\/s41419-026-08591-7","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:34:07Z","timestamp":1774276447000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK\u2012Nrf2 axis in multiple myeloma"],"prefix":"10.1038","volume":"17","author":[{"given":"Peifen","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Shangguan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongliang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0705-6253","authenticated-orcid":false,"given":"Jingjing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7035-6745","authenticated-orcid":false,"given":"Peipei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-2511","authenticated-orcid":false,"given":"Dijun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-1938","authenticated-orcid":false,"given":"Quan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"8591_CR1","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/S0140-6736(21)00135-5","volume":"397","author":"N van de Donk","year":"2021","unstructured":"van de Donk N, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397:410\u201327.","journal-title":"Lancet"},{"key":"8591_CR2","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/s41416-020-01191-y","volume":"124","author":"M Ge","year":"2021","unstructured":"Ge M, Qiao Z, Kong Y, Liang H, Sun Y, Lu H, et al. Modulating proteasome inhibitor tolerance in multiple myeloma: an alternative strategy to reverse inevitable resistance. Br J Cancer. 2021;124:770\u20136.","journal-title":"Br J Cancer"},{"key":"8591_CR3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nrc3257","volume":"12","author":"GJ Morgan","year":"2012","unstructured":"Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012;12:335\u201348.","journal-title":"Nat Rev Cancer"},{"key":"8591_CR4","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.7150\/thno.54453","volume":"12","author":"E Alaterre","year":"2022","unstructured":"Alaterre E, Ovejero S, Herviou L, de Boussac H, Papadopoulos G, Kulis M, et al. Comprehensive characterization of the epigenetic landscape in multiple myeloma. Theranostics. 2022;12:1715\u201329.","journal-title":"Theranostics"},{"key":"8591_CR5","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.3390\/cancers14133270","volume":"14","author":"Y Ohguchi","year":"2022","unstructured":"Ohguchi Y, Ohguchi H. Diverse functions of KDM5 in cancer: transcriptional repressor or activator? Cancers. 2022;14:3270.","journal-title":"Cancers"},{"key":"8591_CR6","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/s41586-023-06254-7","volume":"619","author":"J Li","year":"2023","unstructured":"Li J, Lan Z, Liao W, Horner JW, Xu X, Liu J, et al. Histone demethylase KDM5D upregulation drives sex differences in colon cancer. Nature. 2023;619:632\u20139.","journal-title":"Nature"},{"key":"8591_CR7","doi-asserted-by":"publisher","first-page":"4387","DOI":"10.1172\/JCI91191","volume":"126","author":"B Rondinelli","year":"2016","unstructured":"Rondinelli B, Rosano D, Antonini E, Frenquelli M, Montanini L, Huang D, et al. Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer. J Clin Investig. 2016;126:4387.","journal-title":"J Clin Investig"},{"key":"8591_CR8","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.bbrc.2015.07.049","volume":"464","author":"Q Wang","year":"2015","unstructured":"Wang Q, Wei J, Su P, Gao P. Histone demethylase JARID1C promotes breast cancer metastasis cells via downregulating BRMS1 expression. Biochem Biophys Res Commun. 2015;464:659\u201366.","journal-title":"Biochem Biophys Res Commun"},{"key":"8591_CR9","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004635","volume":"8","author":"HF Shen","year":"2021","unstructured":"Shen HF, Zhang WJ, Huang Y, He YH, Hu GS, Wang L, et al. The dual function of KDM5C in both gene transcriptional activation and repression promotes breast cancer cell growth and tumorigenesis. Adv Sci. 2021;8:2004635.","journal-title":"Adv Sci"},{"key":"8591_CR10","doi-asserted-by":"publisher","first-page":"5567","DOI":"10.1158\/1078-0432.CCR-20-1741","volume":"26","author":"R Tricarico","year":"2020","unstructured":"Tricarico R, Nicolas E, Hall MJ, Golemis EA. X- and Y-linked chromatin-modifying genes as regulators of sex-specific cancer incidence and prognosis. Clin Cancer Res. 2020;26:5567\u201378.","journal-title":"Clin Cancer Res"},{"key":"8591_CR11","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.cell.2016.02.064","volume":"165","author":"H Shen","year":"2016","unstructured":"Shen H, Xu W, Guo R, Rong B, Gu L, Wang Z, et al. Suppression of enhancer overactivation by a Rack7-histone demethylase complex. Cell. 2016;165:331\u201342.","journal-title":"Cell"},{"key":"8591_CR12","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1177\/1533034616629261","volume":"16","author":"L Xu","year":"2017","unstructured":"Xu L, Wu W, Cheng G, Qian M, Hu K, Yin G, et al. Enhancement of proliferation and invasion of gastric cancer cells by KDM5C via a decrease in p53 expression. Technol Cancer Res Treat. 2017;16:141\u20139.","journal-title":"Technol Cancer Res Treat"},{"key":"8591_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.535449","volume":"10","author":"H Lin","year":"2020","unstructured":"Lin H, Ma N, Zhao L, Yang G, Cao B. KDM5c promotes colon cancer cell proliferation through the FBXW7-c-Jun regulatory axis. Front Oncol. 2020;10:535449.","journal-title":"Front Oncol"},{"key":"8591_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01220-7","volume":"19","author":"X Chen","year":"2020","unstructured":"Chen X, Xu M, Xu X, Zeng K, Liu X, Pan B, et al. METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Mol Cancer. 2020;19:106.","journal-title":"Mol Cancer"},{"key":"8591_CR15","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.biopha.2018.08.041","volume":"107","author":"H Lin","year":"2018","unstructured":"Lin H, Yang G, Yu J, Wang J, Li Q, Guo S, et al. KDM5c inhibits multidrug resistance of colon cancer cell line by down-regulating ABCC1. Biomed Pharmacother. 2018;107:1205\u20139.","journal-title":"Biomed Pharmacother"},{"key":"8591_CR16","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.3390\/cancers14081894","volume":"14","author":"AL Lemster","year":"2022","unstructured":"Lemster AL, Sievers E, Pasternack H, Lazar-Karsten P, Kl\u00fcmper N, Sailer V, et al. Histone demethylase KDM5C drives prostate cancer progression by promoting EMT. Cancers. 2022;14:1894.","journal-title":"Cancers"},{"key":"8591_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108793","volume":"114","author":"Z Hong","year":"2019","unstructured":"Hong Z, Wu G, Xiang ZD, Xu CD, Huang SS, Li C, et al. KDM5C is transcriptionally regulated by BRD4 and promotes castration-resistant prostate cancer cell proliferation by repressing PTEN. Biomed Pharmacother. 2019;114:108793.","journal-title":"Biomed Pharmacother"},{"key":"8591_CR18","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1016\/j.ajpath.2014.05.022","volume":"184","author":"J Stein","year":"2014","unstructured":"Stein J, Majores M, Rohde M, Lim S, Schneider S, Krappe E, et al. KDM5C is overexpressed in prostate cancer and is a prognostic marker for prostate-specific antigen-relapse following radical prostatectomy. Am J Pathol. 2014;184:2430\u20137.","journal-title":"Am J Pathol"},{"key":"8591_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1798-4","volume":"15","author":"X Ji","year":"2015","unstructured":"Ji X, Jin S, Qu X, Li K, Wang H, He H, et al. Lysine-specific demethylase 5C promotes hepatocellular carcinoma cell invasion through inhibition of BMP7 expression. BMC Cancer. 2015;15:801.","journal-title":"BMC Cancer"},{"key":"8591_CR20","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1002\/kjm2.12501","volume":"38","author":"X Qian","year":"2022","unstructured":"Qian X, Bao ZM, Yao D, Shi Y. Lysine demethylase 5C epigenetically reduces transcription of ITIH1 that results in augmented progression of liver hepatocellular carcinoma. Kaohsiung J Med Sci. 2022;38:437\u201346.","journal-title":"Kaohsiung J Med Sci"},{"key":"8591_CR21","doi-asserted-by":"publisher","first-page":"2013.0514","DOI":"10.1098\/rstb.2013.0514","volume":"369","author":"E Shen","year":"2014","unstructured":"Shen E, Shulha H, Weng Z, Akbarian S. Regulation of histone H3K4 methylation in brain development and disease. Philos Trans R Soc Lond B Biol Sci. 2014;369:2013.0514.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"8591_CR22","doi-asserted-by":"publisher","first-page":"7776","DOI":"10.1111\/febs.16204","volume":"289","author":"HAM Hatch","year":"2022","unstructured":"Hatch HAM, Secombe J. Molecular and cellular events linking variants in the histone demethylase KDM5C to the intellectual disability disorder Claes-Jensen syndrome. FEBS J. 2022;289:7776\u201387.","journal-title":"FEBS J"},{"key":"8591_CR23","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.trecan.2017.08.004","volume":"3","author":"KM Harmeyer","year":"2017","unstructured":"Harmeyer KM, Facompre ND, Herlyn M, Basu D. JARID1 histone demethylases: emerging targets in cancer. Trends Cancer. 2017;3:713\u201325.","journal-title":"Trends Cancer"},{"key":"8591_CR24","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1007","volume":"7","author":"N Nikesitch","year":"2018","unstructured":"Nikesitch N, Lee JM, Ling S, Roberts TL. Endoplasmic reticulum stress in the development of multiple myeloma and drug resistance. Clin Transl Immunol. 2018;7:e1007.","journal-title":"Clin Transl Immunol"},{"key":"8591_CR25","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.1007\/s00018-021-03756-3","volume":"78","author":"S Xiong","year":"2021","unstructured":"Xiong S, Chng W-J, Zhou J. Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma. Cell Mol Life Sci. 2021;78:3883\u2013906.","journal-title":"Cell Mol Life Sci"},{"key":"8591_CR26","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.3390\/ijms19113503","volume":"19","author":"C-H Yen","year":"2018","unstructured":"Yen C-H, Hsiao H-H. NRF2 is one of the players involved in bone marrow-mediated drug resistance in multiple myeloma. Int J Mol Sci. 2018;19:3503.","journal-title":"Int J Mol Sci"},{"key":"8591_CR27","doi-asserted-by":"publisher","first-page":"29854","DOI":"10.1074\/jbc.M115.664953","volume":"290","author":"B Li","year":"2015","unstructured":"Li B, Fu J, Chen P, Ge X, Li Y, Kuiatse I, et al. The nuclear factor (erythroid-derived 2)-like 2 and proteasome maturation protein axis mediate bortezomib resistance in multiple myeloma. J Biol Chem. 2015;290:29854\u201368.","journal-title":"J Biol Chem"},{"key":"8591_CR28","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.molmed.2016.05.002","volume":"22","author":"S Menegon","year":"2016","unstructured":"Menegon S, Columbano A, Giordano S. The dual roles of NRF2 in cancer. Trends Mol Med. 2016;22:578\u201393.","journal-title":"Trends Mol Med"},{"key":"8591_CR29","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022112012","volume":"41","author":"M Wang","year":"2022","unstructured":"Wang M, Chen ZY, Zhang Y. CBP\/p300 and HDAC activities regulate H3K27 acetylation dynamics and zygotic genome activation in mouse preimplantation embryos. EMBO J. 2022;41:e112012.","journal-title":"EMBO J"},{"key":"8591_CR30","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1016\/j.molcel.2025.05.006","volume":"85","author":"C Lu","year":"2025","unstructured":"Lu C, Bai X, Zhang H, Zhang Y, Yang M, Zheng Y, et al. Mediator regulates transcriptional termination through crosstalk with pre-mRNA 3\u2019 end processing factors. Mol Cell. 2025;85:2147\u201364.e10.","journal-title":"Mol Cell"},{"key":"8591_CR31","doi-asserted-by":"publisher","first-page":"5000","DOI":"10.1093\/nar\/gkac291","volume":"50","author":"F Huang","year":"2022","unstructured":"Huang F, Feng Y, Peterlin BM, Fujinaga K. P-TEFb is degraded by Siah1\/2 in quiescent cells. Nucleic Acids Res. 2022;50:5000\u201313.","journal-title":"Nucleic Acids Res"},{"key":"8591_CR32","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/nchembio.2087","volume":"12","author":"C Johansson","year":"2016","unstructured":"Johansson C, Velupillai S, Tumber A, Szykowska A, Hookway ES, Nowak RP, et al. Structural analysis of human KDM5B guides histone demethylase inhibitor development. Nat Chem Biol. 2016;12:539\u201345.","journal-title":"Nat Chem Biol"},{"key":"8591_CR33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s40618-021-01606-4","volume":"45","author":"Y Wang","year":"2022","unstructured":"Wang Y, Ye H, Yang Y, Li J, Cen A, Zhao L. microRNA-181a promotes the oncogene S100A2 and enhances papillary thyroid carcinoma growth by mediating the expression of histone demethylase KDM5C. J Endocrinol Investig. 2022;45:17\u201328.","journal-title":"J Endocrinol Investig"},{"key":"8591_CR34","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.2147\/OTT.S288799","volume":"14","author":"Q Zhang","year":"2021","unstructured":"Zhang Q, Xu L, Wang J, Zhu X, Ma Z, Yang J, et al. KDM5C expedites lung cancer growth and metastasis through epigenetic regulation of MicroRNA-133a. Onco Targets Ther. 2021;14:1187\u2013204.","journal-title":"Onco Targets Ther"},{"key":"8591_CR35","first-page":"30","volume":"39","author":"Y Cui","year":"2022","unstructured":"Cui Y, Lv C, Wen Y, Zhao D, Yang Y, Qiu H, et al. HOXD3 up-regulating KDM5C promotes malignant progression of diffuse large B-cell lymphoma by decreasing p53 expression. Balk Med J. 2022;39:30\u20138.","journal-title":"Balk Med J"},{"key":"8591_CR36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.664847","volume":"12","author":"XJ Chen","year":"2021","unstructured":"Chen XJ, Ren AQ, Zheng L, Zheng ED. Predictive value of KDM5C alterations for immune checkpoint inhibitors treatment outcomes in patients with cancer. Front Immunol. 2021;12:664847.","journal-title":"Front Immunol"},{"key":"8591_CR37","doi-asserted-by":"publisher","first-page":"231810250","DOI":"10.3390\/ijms231810250","volume":"23","author":"D Drongitis","year":"2022","unstructured":"Drongitis D, Verrillo L, De Marinis P, Orabona P, Caiola A, Turitto G, et al. The chromatin-oxygen sensor gene KDM5C associates with novel hypoxia-related signatures in glioblastoma multiforme. Int J Mol Sci. 2022;23:231810250.","journal-title":"Int J Mol Sci"},{"key":"8591_CR38","doi-asserted-by":"publisher","first-page":"8674","DOI":"10.7150\/thno.60233","volume":"11","author":"Q Zheng","year":"2021","unstructured":"Zheng Q, Li P, Zhou X, Qiang Y, Fan J, Lin Y, et al. Deficiency of the X-inactivation escaping gene KDM5C in clear cell renal cell carcinoma promotes tumorigenicity by reprogramming glycogen metabolism and inhibiting ferroptosis. Theranostics. 2021;11:8674\u201391.","journal-title":"Theranostics"},{"key":"8591_CR39","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3389\/fonc.2020.01025","volume":"10","author":"B Zhang","year":"2020","unstructured":"Zhang B, Zhou BH, Xiao M, Li H, Guo L, Wang MX, et al. KDM5C represses FASN-mediated lipid metabolism to exert tumor suppressor activity in intrahepatic cholangiocarcinoma. Front Oncol. 2020;10:1025.","journal-title":"Front Oncol"},{"key":"8591_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0657-0","volume":"16","author":"IC Salaroglio","year":"2017","unstructured":"Salaroglio IC, Panada E, Moiso E, Buondonno I, Provero P, Rubinstein M, et al. PERK induces resistance to cell death elicited by endoplasmic reticulum stress and chemotherapy. Mol Cancer. 2017;16:91.","journal-title":"Mol Cancer"},{"key":"8591_CR41","doi-asserted-by":"publisher","first-page":"4907","DOI":"10.1182\/blood-2005-08-3531","volume":"107","author":"EA Obeng","year":"2006","unstructured":"Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr, Lee KP, Boise LH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107:4907\u201316.","journal-title":"Blood"},{"key":"8591_CR42","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.1038\/s41388-019-0912-5","volume":"38","author":"J Wang","year":"2019","unstructured":"Wang J, Jiang J, Chen H, Wang L, Guo H, Yang L, et al. FDA-approved drug screen identifies proteasome as a synthetic lethal target in MYC-driven neuroblastoma. Oncogene. 2019;38:6737\u201351.","journal-title":"Oncogene"},{"key":"8591_CR43","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1182\/blood-2006-11-053728","volume":"110","author":"EL Davenport","year":"2007","unstructured":"Davenport EL, Moore HE, Dunlop AS, Sharp SY, Workman P, Morgan GJ, et al. Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Blood. 2007;110:2641\u20139.","journal-title":"Blood"},{"key":"8591_CR44","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.3390\/cancers12102864","volume":"12","author":"T Bagratuni","year":"2020","unstructured":"Bagratuni T, Patseas D, Mavrianou-Koutsoukou N, Liacos CI, Sklirou AD, Rousakis P, et al. Characterization of a PERK kinase inhibitor with anti-myeloma activity. Cancers. 2020;12:2864.","journal-title":"Cancers"},{"key":"8591_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-020-00253-3","volume":"9","author":"M Caillot","year":"2020","unstructured":"Caillot M, Bourgeais J, Dakik H, Coste E, Mazure NM, Lelievre E, et al. Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells. Oncogenesis. 2020;9:68.","journal-title":"Oncogenesis"},{"key":"8591_CR46","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3390\/cancers12020333","volume":"12","author":"AM Martelli","year":"2020","unstructured":"Martelli AM, Paganelli F, Chiarini F, Evangelisti C, McCubrey JA. The unfolded protein response: a novel therapeutic target in acute leukemias. Cancers. 2020;12:333.","journal-title":"Cancers"},{"key":"8591_CR47","doi-asserted-by":"publisher","first-page":"5340","DOI":"10.3390\/cancers14215340","volume":"14","author":"G Wang","year":"2022","unstructured":"Wang G, Fan F, Sun C, Hu Y. Looking into Endoplasmic Reticulum Stress: the key to drug-resistance of multiple myeloma? Cancers. 2022;14:5340.","journal-title":"Cancers"},{"key":"8591_CR48","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.celrep.2013.02.030","volume":"3","author":"NS Outchkourov","year":"2013","unstructured":"Outchkourov NS, Mui\u00f1o JM, Kaufmann K, van Ijcken WF, Groot Koerkamp MJ, van Leenen D, et al. Balancing of histone H3K4 methylation states by the Kdm5c\/SMCX histone demethylase modulates promoter and enhancer function. Cell Rep. 2013;3:1071\u20139.","journal-title":"Cell Rep"},{"key":"8591_CR49","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02475-4","volume":"22","author":"KL Liu","year":"2022","unstructured":"Liu KL, Yin YW, Lu BS, Niu YL, Wang DD, Shi B, et al. E2F6\/KDM5C promotes SF3A3 expression and bladder cancer progression through a specific hypomethylated DNA promoter. Cancer Cell Int. 2022;22:109.","journal-title":"Cancer Cell Int"},{"key":"8591_CR50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63886","volume":"10","author":"HAM Hatch","year":"2021","unstructured":"Hatch HAM, Belalcazar HM, Marshall OJ, Secombe J. A KDM5-prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation. Elife. 2021;10:e63886.","journal-title":"Elife"},{"key":"8591_CR51","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1002\/cmdc.202000933","volume":"16","author":"T Iida","year":"2021","unstructured":"Iida T, Itoh Y, Takahashi Y, Yamashita Y, Kurohara T, Miyake Y, et al. Design, synthesis, and biological evaluation of lysine demethylase 5 c degraders. ChemMedChem. 2021;16:1609\u201318.","journal-title":"ChemMedChem"},{"key":"8591_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00988-5","volume":"8","author":"J Ju","year":"2017","unstructured":"Ju J, Chen A, Deng Y, Liu M, Wang Y, Wang Y, et al. NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Slug expression. Nat Commun. 2017;8:928.","journal-title":"Nat Commun"},{"key":"8591_CR53","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.7150\/jca.69216","volume":"13","author":"P Lu","year":"2022","unstructured":"Lu P, Yu Z, Wang K, Zhai Y, Chen B, Liu M, et al. DDX21 interacts with WDR5 to promote colorectal cancer cell proliferation by activating CDK1 expression. J Cancer. 2022;13:1530\u20139.","journal-title":"J Cancer"},{"key":"8591_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102647","volume":"61","author":"X Liu","year":"2023","unstructured":"Liu X, Qin H, Zhang L, Jia C, Chao Z, Qin X, et al. Hyperoxia induces glucose metabolism reprogramming and intracellular acidification by suppressing the MYC\/MCT1 axis in lung cancer. Redox Biol. 2023;61:102647.","journal-title":"Redox Biol"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08591-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08591-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08591-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T20:02:35Z","timestamp":1774987355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08591-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8591"],"URL":"https:\/\/doi.org\/10.1038\/s41419-026-08591-7","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"1 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The animal studies were approved by the Committee on Animal Research and Ethics of Nanjing University (IACUC-2205008), and all the protocols conformed to the Guidelines for Ethical Conduct in the Care and Use of Nonhuman Animals in Research. Collection of CD138\n                      +\n                      primary patient cells was approved by the Ethics Committee of Jinling Hospital (2019NZKYKS-001-01). All the participating individuals signed informed consent forms.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}],"article-number":"339"}}