{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:19:18Z","timestamp":1758673158949,"version":"3.44.0"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Curcumin, a polyphenolic compound derived from the plant <jats:italic>Curcuma longa<\/jats:italic> L., has demonstrated a wide range of therapeutic properties, including potential anticancer effects. However, its clinical efficacy is limited due to poor bioavailability and stability. To overcome these challenges, curcumin analogs like EF-24 have been developed with improved pharmacological properties. In this study, in order to improve our understanding of EF-24\u2019s potential mechanisms of action, we used whole-transcriptome sequencing to identify genome-wide functional impacts of EF-24 treatment in leukemia cells. These results enabled the development of a testable model system for associating druggable genes with clinical disease targets related to EF-24 treatment. To develop our model of the transcriptional response to EF-24 treatment, we used four well studied model cell lines for leukemia research, specifically the chronic myeloid leukemia (CML) cell line K-562 and acute myeloid leukemia (AML) cell lines HL-60, Kasumi-1, and THP-1. Cell viability was significantly decreased in all four of these leukemia models following EF-24 treatment as compared to untreated controls. We discovered that the genes ATF3, CLU, HSPA6, OSGIN1, ZFAND2A, and CXCL8, which are associated with reduced cell viability and proliferation, were consistently upregulated in all EF-24\u2013treated cell lines. Further analysis of the tested cell lines revealed the activation of various signaling pathways, but notably the S100 family signaling pathway was consistently activated in all four cell lines. Our results provide critical insights into the molecular underpinnings of EF-24\u2019s antitumor efficacy against leukemia subtypes, highlighting its multifaceted impact on signaling pathways and gene networks that regulate cell survival, proliferation, and immune responses in cell line models of myeloid leukemia subtypes.<\/jats:p>","DOI":"10.1371\/journal.pone.0330906","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T17:44:07Z","timestamp":1758649447000},"page":"e0330906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic discovery of EF-24 targets unveils antitumorigenic mechanisms in leukemia cells"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0318-2167","authenticated-orcid":true,"given":"Ajeet P.","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah","family":"Wax","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana S.","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-4256","authenticated-orcid":true,"given":"Jonathan L.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"pone.0330906.ref001","volume-title":"Leukemia","author":"A Chennamadhavuni","year":"2024"},{"issue":"3","key":"pone.0330906.ref002","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s43018-021-00192-x","article-title":"Advancing cancer therapy","volume":"2","year":"2021","journal-title":"Nat Cancer"},{"issue":"12","key":"pone.0330906.ref003","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.3390\/pharmaceutics13122102","article-title":"Biomedical applications and bioavailability of curcumin-an updated overview","volume":"13","author":"S-I Sohn","year":"2021","journal-title":"Pharmaceutics"},{"key":"pone.0330906.ref004","doi-asserted-by":"crossref","first-page":"614","DOI":"10.3389\/fonc.2018.00614","article-title":"Bioactivities of EF24, a novel curcumin analog: a review","volume":"8","author":"Y He","year":"2018","journal-title":"Front Oncol"},{"issue":"8","key":"pone.0330906.ref005","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.3390\/cancers12082163","article-title":"The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells","volume":"12","author":"P-C Hsiao","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"11","key":"pone.0330906.ref006","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.3390\/ijms18112289","article-title":"Apoptosis Induced by the Curcumin Analogue EF-24 Is Neither Mediated by Oxidative Stress-Related Mechanisms nor Affected by Expression of Main Drug Transporters ABCB1 and ABCG2 in Human Leukemia Cells","volume":"18","author":"N Skoupa","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0330906.ref007","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0229104","article-title":"Adaptive phenotypic modulations lead to therapy resistance in chronic myeloid leukemia cells","volume":"15","author":"S Baykal-K\u00f6se","year":"2020","journal-title":"PLoS One"},{"issue":"3","key":"pone.0330906.ref008","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1182\/blood.V56.3.344.344","article-title":"Human myeloid leukemia cell lines: a review","volume":"56","author":"HP Koeffler","year":"1980","journal-title":"Blood"},{"issue":"6","key":"pone.0330906.ref009","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.3390\/ijms24065377","article-title":"Choosing the right cell line for acute myeloid leukemia (AML) research","volume":"24","author":"R Skopek","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pone.0330906.ref010","doi-asserted-by":"crossref","first-page":"155161","DOI":"10.1016\/j.prp.2024.155161","article-title":"The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia","volume":"254","author":"M El-Tanani","year":"2024","journal-title":"Pathol Res Pract"},{"issue":"5942","key":"pone.0330906.ref011","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/306492a0","article-title":"Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite","volume":"306","author":"PH Reitsma","year":"1983","journal-title":"Nature"},{"key":"pone.0330906.ref012","doi-asserted-by":"crossref","first-page":"1060537","DOI":"10.3389\/fcell.2023.1060537","article-title":"Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model","volume":"11","author":"J Basu","year":"2023","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"pone.0330906.ref013","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/10428190400007565","article-title":"The Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia","volume":"46","author":"L Larizza","year":"2005","journal-title":"Leuk Lymphoma"},{"issue":"1","key":"pone.0330906.ref014","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.intimp.2014.08.002","article-title":"THP-1 cell line: an in vitro cell model for immune modulation approach","volume":"23","author":"W Chanput","year":"2014","journal-title":"Int Immunopharmacol"},{"issue":"8","key":"pone.0330906.ref015","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12082163","article-title":"The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells.","volume":"12","author":"PC Hsiao","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"8","key":"pone.0330906.ref016","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.3390\/cancers12082037","article-title":"Friend or Foe: S100 proteins in cancer","volume":"12","author":"C Allg\u00f6wer","year":"2020","journal-title":"Cancers (Basel)"},{"key":"pone.0330906.ref017","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10735-006-9052-7","article-title":"Clusterin and DNA repair: a new function in cancer for a key player in apoptosis and cell cycle control","volume":"37","author":"B Shannan","year":"2006","journal-title":"J Mol Histol"},{"issue":"1","key":"pone.0330906.ref018","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s41392-022-01110-y","article-title":"Regulated cell death (RCD) in cancer: key pathways and targeted therapies","volume":"7","author":"F Peng","year":"2022","journal-title":"Signal Transduct Target Ther"},{"issue":"22","key":"pone.0330906.ref019","doi-asserted-by":"crossref","first-page":"12426","DOI":"10.3390\/ijms222212426","article-title":"Contribution of the Transcription Factors Sp1\/Sp3 and AP-1 to Clusterin Gene Expression during Corneal Wound Healing of Tissue-Engineered Human Corneas","volume":"22","author":"C Gross","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"21","key":"pone.0330906.ref020","doi-asserted-by":"crossref","first-page":"7187","DOI":"10.12998\/wjcc.v10.i21.7187","article-title":"Effects of glucocorticoids on leukocytes: genomic and non-genomic mechanisms","volume":"10","author":"W-Y Jia","year":"2022","journal-title":"World J Clin Cases"},{"key":"pone.0330906.ref021","doi-asserted-by":"crossref","first-page":"756094","DOI":"10.3389\/fgene.2021.756094","article-title":"SERPINH1 is a potential prognostic biomarker and correlated with immune infiltration: a pan-cancer analysis","volume":"12","author":"Y Wang","year":"2022","journal-title":"Front Genet"},{"key":"pone.0330906.ref022","doi-asserted-by":"crossref","first-page":"1108167","DOI":"10.3389\/fgene.2023.1108167","article-title":"ANXA2 is a potential biomarker for cancer prognosis and immune infiltration: a systematic pan-cancer analysis","volume":"14","author":"Y Ning","year":"2023","journal-title":"Front Genet"},{"issue":"9","key":"pone.0330906.ref023","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/nrc2460","article-title":"A new MAFia in cancer","volume":"8","author":"A Eych\u00e8ne","year":"2008","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"pone.0330906.ref024","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1038\/s41467-021-23752-2","article-title":"Targeted PI3K\/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia","volume":"12","author":"V Ecker","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0330906.ref025","doi-asserted-by":"crossref","first-page":"658315","DOI":"10.3389\/fimmu.2021.658315","article-title":"The Diverse Roles of Heme Oxygenase-1 in Tumor Progression","volume":"12","author":"KN Luu Hoang","year":"2021","journal-title":"Front Immunol"},{"issue":"4","key":"pone.0330906.ref026","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3892\/ijo.2021.5257","article-title":"Sequestosome 1\/p62: a multitasker in the regulation of malignant tumor aggression (Review)","volume":"59","author":"J Tang","year":"2021","journal-title":"Int J Oncol"},{"key":"pone.0330906.ref027","doi-asserted-by":"crossref","first-page":"667995","DOI":"10.3389\/fonc.2021.667995","article-title":"RNA-Sequencing Reveals Heat Shock 70-kDa Protein 6 (HSPA6) as a Novel Thymoquinone-Upregulated Gene That Inhibits Growth, Migration, and Invasion of Triple-Negative Breast Cancer Cells","volume":"11","author":"S Shen","year":"2021","journal-title":"Front Oncol"},{"issue":"1","key":"pone.0330906.ref028","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41420-022-00902-z","article-title":"The NSUN5-FTH1\/FTL pathway mediates ferroptosis in bone marrow-derived mesenchymal stem cells","volume":"8","author":"J Liu","year":"2022","journal-title":"Cell Death Discov"},{"issue":"6","key":"pone.0330906.ref029","article-title":"TSPYL2 is important for G1 checkpoint maintenance upon DNA damage","volume":"6","author":"KP Tao","year":"2011","journal-title":"PLoS One"},{"issue":"4","key":"pone.0330906.ref030","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.cmet.2024.01.006","article-title":"PHLDA2-mediated phosphatidic acid peroxidation triggers a distinct ferroptotic response during tumor suppression","volume":"36","author":"X Yang","year":"2024","journal-title":"Cell Metab"},{"issue":"1","key":"pone.0330906.ref031","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12967-023-04017-6","article-title":"Immunogenic cell death in cancer: concept and therapeutic implications","volume":"21","author":"L Galluzzi","year":"2023","journal-title":"J Transl Med"},{"issue":"1","key":"pone.0330906.ref032","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41392-021-00766-2","article-title":"ELANE: an emerging lane to selective anticancer therapy","volume":"6","author":"B Peng","year":"2021","journal-title":"Signal Transduct Target Ther"},{"issue":"7","key":"pone.0330906.ref033","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.7150\/ijbs.82000","article-title":"CTSG suppresses colorectal cancer progression through negative regulation of Akt\/mTOR\/Bcl2 signaling pathway","volume":"19","author":"S Chan","year":"2023","journal-title":"Int J Biol Sci"},{"issue":"1","key":"pone.0330906.ref034","article-title":"MLC1 overexpression inhibits tumor progression through PI3K\/AKT signal pathway in prostate cancer","volume":"8","author":"Z Wu","year":"2024","journal-title":"Adv Biol (Weinh)"},{"key":"pone.0330906.ref035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-35723-8_1","article-title":"Neutrophils in the tumor microenvironment","volume":"1224","author":"L Wu","year":"2020","journal-title":"Adv Exp Med Biol"},{"issue":"2","key":"pone.0330906.ref036","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3390\/ijms22020603","article-title":"The multifaced role of STAT3 in cancer and its implication for anticancer therapy","volume":"22","author":"M Tolomeo","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"5","key":"pone.0330906.ref037","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1093\/nar\/gkt1232","article-title":"Analysis of the SWI\/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation","volume":"42","author":"AP Singh","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0330906.ref038","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1158\/2326-6066.CIR-13-0214","article-title":"IL-10: master switch from tumor-promoting inflammation to antitumor immunity","volume":"2","author":"M Oft","year":"2014","journal-title":"Cancer Immunol Res"},{"issue":"1","key":"pone.0330906.ref039","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12079-015-0302-x","article-title":"A network map of Interleukin-10 signaling pathway","volume":"10","author":"R Verma","year":"2016","journal-title":"J Cell Commun Signal"},{"issue":"4","key":"pone.0330906.ref040","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1089\/jir.2012.0110","article-title":"Interferons as inducers of apoptosis in malignant cells","volume":"33","author":"KP Kotredes","year":"2013","journal-title":"J Interferon Cytokine Res"},{"issue":"11","key":"pone.0330906.ref041","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/s41419-020-03221-2","article-title":"Detection of immunogenic cell death and its relevance for cancer therapy","volume":"11","author":"J Fucikova","year":"2020","journal-title":"Cell Death Dis"},{"issue":"12","key":"pone.0330906.ref042","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1002\/1878-0261.12851","article-title":"Targeting immunogenic cell death in cancer","volume":"14","author":"A Ahmed","year":"2020","journal-title":"Mol Oncol"},{"issue":"5","key":"pone.0330906.ref043","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/s41418-022-00996-z","article-title":"Of the many cellular responses activated by TP53, which ones are critical for tumour suppression?","volume":"29","author":"AF Thomas","year":"2022","journal-title":"Cell Death Differ"},{"issue":"1","key":"pone.0330906.ref044","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3026(17)30233-8","article-title":"The global burden of haematological diseases","volume":"5","author":"The Lancet Haematology","year":"2018","journal-title":"Lancet Haematol"},{"issue":"10147","key":"pone.0330906.ref045","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0140-6736(18)31041-9","article-title":"Acute myeloid leukaemia","volume":"392","author":"NJ Short","year":"2018","journal-title":"Lancet"},{"issue":"11","key":"pone.0330906.ref046","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.3390\/biom12111636","article-title":"Curcumin and its analogs in non-small cell lung cancer treatment: challenges and expectations","volume":"12","author":"C Tang","year":"2022","journal-title":"Biomolecules"},{"issue":"20","key":"pone.0330906.ref047","doi-asserted-by":"crossref","first-page":"6302","DOI":"10.3390\/molecules26206302","article-title":"Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer","volume":"26","author":"V Ib\u00e1\u00f1ez Gaspar","year":"2021","journal-title":"Molecules"},{"issue":"23","key":"pone.0330906.ref048","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.3390\/molecules24234386","article-title":"Curcumin and its derivatives as potential therapeutic agents in prostate, colon and breast cancers","volume":"24","author":"Z Mbese","year":"2019","journal-title":"Molecules"},{"issue":"12","key":"pone.0330906.ref049","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.3390\/molecules24122202","article-title":"Biological effects of EF24, a curcumin derivative, alone or combined with mitotane in adrenocortical tumor cell lines","volume":"24","author":"L Bertazza","year":"2019","journal-title":"Molecules"},{"issue":"6","key":"pone.0330906.ref050","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41584-020-0419-z","article-title":"Translating IL-6 biology into effective treatments","volume":"16","author":"EH Choy","year":"2020","journal-title":"Nat Rev Rheumatol"},{"issue":"21","key":"pone.0330906.ref051","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.3390\/cancers14215270","article-title":"Tumor necrosis factor: what is in a name?","volume":"14","author":"X Wang","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"14","key":"pone.0330906.ref052","doi-asserted-by":"crossref","first-page":"18050","DOI":"10.18632\/oncotarget.7633","article-title":"EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells","volume":"7","author":"P Zou","year":"2016","journal-title":"Oncotarget"},{"issue":"14","key":"pone.0330906.ref053","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1016\/j.bmc.2004.05.006","article-title":"Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents","volume":"12","author":"BK Adams","year":"2004","journal-title":"Bioorg Med Chem"},{"issue":"3","key":"pone.0330906.ref054","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1124\/mol.108.046201","article-title":"Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin","volume":"74","author":"AL Kasinski","year":"2008","journal-title":"Mol Pharmacol"},{"issue":"15","key":"pone.0330906.ref055","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.4161\/cc.6410","article-title":"EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1","volume":"7","author":"SL Thomas","year":"2008","journal-title":"Cell Cycle"},{"issue":"5","key":"pone.0330906.ref056","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/hep.26224","article-title":"Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1\u03b1 inhibition in hepatocellular carcinoma","volume":"57","author":"Y Liang","year":"2013","journal-title":"Hepatology"},{"issue":"1","key":"pone.0330906.ref057","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/sj.cdd.4401779","article-title":"Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer","volume":"13","author":"B Shannan","year":"2006","journal-title":"Cell Death Differ"},{"key":"pone.0330906.ref058","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.2147\/OTT.S201799","article-title":"Progression of the role of CRYAB in signaling pathways and cancers","volume":"12","author":"J Zhang","year":"2019","journal-title":"Onco Targets Ther"},{"issue":"3","key":"pone.0330906.ref059","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcp.22836","article-title":"Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain","volume":"227","author":"N Kim","year":"2012","journal-title":"J Cell Physiol"},{"issue":"5","key":"pone.0330906.ref060","doi-asserted-by":"crossref","first-page":"992","DOI":"10.3390\/biomedicines10050992","article-title":"Oxidative Stress-Induced Growth Inhibitor (OSGIN1), a Target of X-Box-Binding Protein 1, Protects Palmitic Acid-Induced Vascular Lipotoxicity through Maintaining Autophagy","volume":"10","author":"C-S Khoi","year":"2022","journal-title":"Biomedicines"},{"issue":"2","key":"pone.0330906.ref061","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1158\/1535-7163.233.4.2","article-title":"Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin","volume":"4","author":"C Yan","year":"2005","journal-title":"Mol Cancer Ther"},{"issue":"23","key":"pone.0330906.ref062","doi-asserted-by":"crossref","first-page":"5739","DOI":"10.3390\/cancers14235739","article-title":"NDRG1 in Cancer: A Suppressor, Promoter, or Both?","volume":"14","author":"V Joshi","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"7","key":"pone.0330906.ref063","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41389-021-00341-y","article-title":"Guanylate-binding proteins induce apoptosis of leukemia cells by regulating MCL-1 and BAK","volume":"10","author":"Y Luo","year":"2021","journal-title":"Oncogenesis"},{"issue":"2","key":"pone.0330906.ref064","doi-asserted-by":"crossref","first-page":"100930","DOI":"10.1016\/j.jbc.2021.100930","article-title":"STING-mediated degradation of IFI16 negatively regulates apoptosis by inhibiting p53 phosphorylation at serine 392","volume":"297","author":"D Li","year":"2021","journal-title":"J Biol Chem"},{"issue":"3","key":"pone.0330906.ref065","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41416-021-01400-2","article-title":"Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy","volume":"125","author":"E Schaafsma","year":"2021","journal-title":"Br J Cancer"},{"issue":"9","key":"pone.0330906.ref066","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41419-023-06164-6","article-title":"Crotonylated BEX2 interacts with NDP52 and enhances mitophagy to modulate chemotherapeutic agent-induced apoptosis in non-small-cell lung cancer cells","volume":"14","author":"N Mu","year":"2023","journal-title":"Cell Death Dis"},{"issue":"1","key":"pone.0330906.ref067","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1038\/s41598-024-53015-1","article-title":"Identification of VWA5A as a novel biomarker for inhibiting metastasis in breast cancer by machine-learning based protein prioritization","volume":"14","author":"J Koh","year":"2024","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0330906.ref068","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3390\/brainsci12060763","article-title":"PTPRN serves as a prognostic biomarker and correlated with immune infiltrates in low grade glioma","volume":"12","author":"P Li","year":"2022","journal-title":"Brain Sci"},{"issue":"5","key":"pone.0330906.ref069","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.trecan.2023.02.001","article-title":"Cell death, therapeutics, and the immune response in cancer","volume":"9","author":"K H\u00e4nggi","year":"2023","journal-title":"Trends Cancer"},{"issue":"9","key":"pone.0330906.ref070","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s41419-018-0919-9","article-title":"Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells","volume":"9","author":"FO Enane","year":"2018","journal-title":"Cell Death Dis"},{"issue":"4","key":"pone.0330906.ref071","doi-asserted-by":"crossref","first-page":"546","DOI":"10.3181\/00379727-166-41106","article-title":"A multipotential leukemia cell line (K-562) of human origin","volume":"166","author":"BB Lozzio","year":"1981","journal-title":"Proc Soc Exp Biol Med"},{"issue":"10","key":"pone.0330906.ref072","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1080\/21645515.2020.1717185","article-title":"Targeting interleukin-10 signalling for cancer immunotherapy, a promising and complicated task","volume":"16","author":"G Ni","year":"2020","journal-title":"Hum Vaccin Immunother"},{"key":"pone.0330906.ref073","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1080\/07357907.2018.1533965","article-title":"Tumor suppression by the EGR1, DMP1, ARF, p53, and PTEN Network","volume":"36","author":"K Inoue","year":"2018","journal-title":"Cancer Invest"},{"issue":"15","key":"pone.0330906.ref074","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1128\/MCB.01101-15","article-title":"Brg1 enables rapid growth of the early embryo by suppressing genes that regulate apoptosis and cell growth arrest","volume":"36","author":"AP Singh","year":"2016","journal-title":"Mol Cell Biol"},{"issue":"6","key":"pone.0330906.ref075","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.1074\/jbc.M110.195040","article-title":"Differential glucocorticoid receptor-mediated transcription mechanisms","volume":"286","author":"S Aoyagi","year":"2011","journal-title":"J Biol Chem"},{"key":"pone.0330906.ref076","doi-asserted-by":"crossref","first-page":"101510","DOI":"10.1016\/j.tranon.2022.101510","article-title":"Key signal transduction pathways and crosstalk in cancer: Biological and therapeutic opportunities","volume":"26","author":"D Fu","year":"2022","journal-title":"Transl Oncol"},{"issue":"1","key":"pone.0330906.ref077","doi-asserted-by":"crossref","first-page":"6369","DOI":"10.1038\/s41467-025-61567-7","article-title":"Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33\/IL1RL1 pathway","volume":"16","author":"D Fu","year":"2025","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0330906.ref078","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190418","article-title":"Biology and therapeutic potential of interleukin-10","volume":"217","author":"M Saraiva","year":"2020","journal-title":"J Exp Med"},{"issue":"1","key":"pone.0330906.ref079","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41392-024-01868-3","article-title":"Targeting cytokine and chemokine signaling pathways for cancer therapy","volume":"9","author":"M Yi","year":"2024","journal-title":"Signal Transduct Target Ther"},{"issue":"11","key":"pone.0330906.ref080","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1111\/j.1745-7254.2008.00889.x","article-title":"Tumor necrosis factor and cancer, buddies or foes?","volume":"29","author":"X Wang","year":"2008","journal-title":"Acta Pharmacol Sin"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T17:44:22Z","timestamp":1758649462000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330906"}},"subtitle":[],"editor":[{"given":"Kota V","family":"Ramana","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":80,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0330906","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,23]]}}}