{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:55:42Z","timestamp":1790474142269,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer is a leading cause of death among the various diseases encountered in humans. Cancer is not a single entity and consists of numerous different types and subtypes that require various treatment regimens. In the last decade, several milestones in cancer treatments were accomplished, such as specific targeting agents or revitalizing the dormant anti-tumor immune response. These milestones have resulted in significant positive clinical responses as well as tumor regression and the prolongation of survival in subsets of cancer patients. Hence, in non-responding patients and non-responding relapsed patients, cancers develop intrinsic mechanisms of resistance to cell death via the overexpression of anti-apoptotic gene products. In parallel, the majority of resistant cancers have been reported to overexpress a transcription factor, Yin Yang 1 (YY1), which regulates the chemo-immuno-resistance of cancer cells to therapeutic anticancer cytotoxic agents. The relationship between the overexpression of YY1 and several anti-apoptotic gene products, such as B-cell lymphoma 2 protein (Bcl-2), B-cell lymphoma extra-large (Bcl-xL), myeloid cell leukemia 1 (Mcl-1) and survivin, is investigated in this paper. The findings demonstrate that these anti-apoptotic gene products are regulated, in part, by YY1 at the transcriptional, epigenetic, post-transcriptional and translational levels. While targeting each of the anti-apoptotic gene products individually has been examined and clinically tested for some, this targeting strategy is not effective due to compensation by other overexpressed anti-apoptotic gene products. In contrast, targeting YY1 directly, through small interfering RNAs (siRNAs), gene editing or small molecule inhibitors, can be therapeutically more effective and generalized in YY1-overexpressed resistant cancers.<\/jats:p>","DOI":"10.3390\/cancers15174267","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:42:20Z","timestamp":1692952940000},"page":"4267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Role of YY1 in the Regulation of Anti-Apoptotic Gene Products in Drug-Resistant Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Megan","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indy","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bonavida","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/0092-8674(91)90189-6","article-title":"Transcriptional repression by YY1, a human GLI-Kr\u00fcppel-related protein, and relief of repression by adenovirus E1A protein","volume":"67","author":"Shi","year":"1991","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12019","DOI":"10.1093\/nar\/gkac230","article-title":"YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency","volume":"50","author":"Dong","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.drup.2019.04.001","article-title":"YY1 regulates cancer cell immune resistance by modulating PD-L1 expression","volume":"43","author":"Hays","year":"2019","journal-title":"Drug Resist. Updates"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17750","DOI":"10.1074\/jbc.M310532200","article-title":"YY1AP, a novel co-activator of YY1","volume":"279","author":"Wang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eaaw2050","DOI":"10.1126\/scitranslmed.aaw2050","article-title":"Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGF\u03b21","volume":"11","author":"Gao","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1128\/MCB.23.13.4494-4510.2003","article-title":"Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein\u2013induced cell differentiation","volume":"23","author":"Kurisaki","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"592164","DOI":"10.3389\/fcell.2020.592164","article-title":"The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1","volume":"8","author":"Verheul","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1615\/CritRevOncog.v16.i3-4.20","article-title":"Mechanisms of Yin Yang 1 in Oncogenesis: The Importance of Indirect Effects","volume":"16","author":"Atchison","year":"2011","journal-title":"Crit. Rev. Oncog."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.3389\/fonc.2019.01230","article-title":"The Two Sides of YY1 in Cancer: A Friend and a Foe","volume":"9","author":"Sarvagalla","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.drup.2017.01.001","article-title":"Inverse correlation between the metastasis suppressor RKIP and the metastasis inducer YY1: Contrasting roles in the regulation of chemo\/immuno\u2013resistance in cancer","volume":"30","author":"Wottrich","year":"2017","journal-title":"Drug Resist. Updates"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/1873-3468.13431","article-title":"Functional analysis of YY1 zinc fingers through cysteine mutagenesis","volume":"593","author":"Chen","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.cell.2017.11.008","article-title":"YY1 Is a Structural Regulator of Enhancer-Promoter Loops","volume":"171","author":"Weintraub","year":"2017","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"504","DOI":"10.2174\/1568009618666181031153151","article-title":"Characterization of YY1 OPB Peptide for its Anticancer Activity","volume":"19","author":"Qi","year":"2019","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_14","unstructured":"Beyrouthy, M.J. (2023, February 20). Subcellular Localization of the Transcription Factor YY1 during Cellular Life and Death. Available online: https:\/\/diginole.lib.fsu.edu\/islandora\/object\/fsu%3A175927\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1128\/MCB.20.14.5096-5106.2000","article-title":"ATF6 as a Transcription Activator of the Endoplasmic Reticulum Stress Element: Thapsigargin Stress-Induced Changes and Synergistic Interactions with NF-Y and YY1","volume":"20","author":"Li","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s13238-016-0306-1","article-title":"Human INO80\/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells","volume":"7","author":"Su","year":"2016","journal-title":"Protein Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jcb.21616","article-title":"The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes","volume":"104","author":"Li","year":"2008","journal-title":"J. Cell Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Potluri, V., Noothi, S.K., Vallabhapurapu, S.D., Yoon, S.O., Driscoll, J.J., Lawrie, C.H., and Vallabhapurapu, S. (2013). Transcriptional Repression of Bim by a Novel YY1-RelA Complex Is Essential for the Survival and Growth of Multiple Myeloma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066121"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kim, J.D., Yu, S., and Kim, J. (2009). YY1 is autoregulated through its own DNA-binding sites. BMC Mol. Biol., 10.","DOI":"10.1186\/1471-2199-10-85"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1128\/MCB.02020-06","article-title":"NF-\u03baB Regulation of YY1 Inhibits Skeletal Myogenesis through Transcriptional Silencing of Myofibrillar Genes","volume":"27","author":"Wang","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/B978-0-12-394387-3.00006-9","article-title":"Chapter Six\u2014Histone Deacetylase Inhibitors and Rational Combination Therapies","volume":"Volume 116","author":"Grant","year":"2012","journal-title":"Advances in Cancer Research [Internet]"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20059","DOI":"10.1038\/srep20059","article-title":"A novel NF-\u03baB\/YY1\/microRNA-10a regulatory circuit in fibroblast-like synoviocytes regulates inflammation in rheumatoid arthritis","volume":"6","author":"Mu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vivarelli, S., Falzone, L., Grillo, C.M., Bonavida, B., Crimi, C., La Mantia, I., and Libra, M. (2022). Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer. Cancers, 14.","DOI":"10.3390\/cancers14040922"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1615\/CritRevOncog.2014011929","article-title":"RKIP-Mediated Chemo-Immunosensitization of Resistant Cancer Cells via Disruption of the NF-\u03baB\/Snail\/YY1\/RKIP Resistance-Driver Loop","volume":"19","author":"Bonavida","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"248","DOI":"10.5483\/BMBRep.2020.53.5.222","article-title":"Human transcription factor YY1 could upregulate the HIV-1 gene expression","volume":"53","author":"Yu","year":"2020","journal-title":"BMB Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"40583","DOI":"10.18632\/oncotarget.17196","article-title":"YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor","volume":"8","author":"Dong","year":"2017","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"21718","DOI":"10.1038\/srep21718","article-title":"Regulation of Transcription Factor Yin Yang 1 by SET7\/9-mediated Lysine Methylation","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Hirashi, Z., Gao, T., Scaffidi, C., Fey, M., Murray, S., Low, A., Pushkareva, O., Rizkallah, R., Deplancke, B., and Verdeguer, F. (2021). A YY1 phosphorylation switch in brown adipose tissue orchestrates energy homeostasis. Nat. Portf.","DOI":"10.21203\/rs.3.rs-523586\/v1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4766","DOI":"10.1091\/mbc.e09-04-0264","article-title":"Regulation of the Transcription Factor YY1 in Mitosis through Phosphorylation of Its DNA-binding Domain","volume":"20","author":"Rizkallah","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1038\/ncomms3598","article-title":"Smurf2 suppresses B-cell proliferation and lymphomagenesis by mediating ubiquitination and degradation of YY1","volume":"4","author":"Ramkumar","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.omtn.2021.04.013","article-title":"Enhancement of myogenic differentiation and inhibition of rhabdomyosarcoma progression by miR-28-3p and miR-193a-5p regulated by SNAIL","volume":"24","author":"Skrzypek","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10001","DOI":"10.7150\/thno.47491","article-title":"Dysregulated Kras\/YY1\/ZNF322A\/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression","volume":"10","author":"Lin","year":"2020","journal-title":"Theranostics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1158\/0008-5472.CAN-16-1898","article-title":"KRAS\/NF-\u03baB\/YY1\/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis","volume":"77","author":"Yuan","year":"2017","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1172\/JCI66553","article-title":"CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia","volume":"123","author":"Chen","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1080\/10428194.2018.1448083","article-title":"Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance (MDR1) gene","volume":"59","author":"Vega","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kora\u0107, P., Antica, M., and Matuli\u0107, M. (2021). MiR-7 in Cancer Development. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030325"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10084","DOI":"10.1038\/s41598-017-10935-5","article-title":"Aurora A Phosphorylation of YY1 during Mitosis Inactivates its DNA Binding Activity","volume":"7","author":"Alexander","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14046","DOI":"10.1074\/jbc.M300789200","article-title":"YY1 is regulated by O-linked N-acetylglucosaminylation (O-glcNAcylation)","volume":"278","author":"Hiromura","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_39","first-page":"1121","article-title":"O-GlcNAcylation of YY1 stimulates tumorigenesis in colorectal cancer cells by targeting SLC22A15 and AANAT","volume":"40","author":"Zhu","year":"2019","journal-title":"Carcinogenesis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1016\/j.bbamcr.2014.04.023","article-title":"Smurf2 regulates the degradation of YY1","volume":"1843","author":"Jeong","year":"2014","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/s41419-021-03956-6","article-title":"MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells","volume":"12","author":"Fu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rizkallah, R., Alexander, K.E., Kassardjian, A., L\u00fcscher, B., and Hurt, M.M. (2011). The Transcription Factor YY1 Is a Substrate for Polo-Like Kinase 1 at the G2\/M Transition of the Cell Cycle. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015928"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1615\/CritRevOncog.v16.i3-4.30","article-title":"The oncogenic role of Yin Yang 1","volume":"16","author":"Zhang","year":"2011","journal-title":"Crit. Rev. Oncog."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1615\/CritRevOncog.2017020959","article-title":"The Multilayered Regulation of the Oncogenic Protein YY1","volume":"22","author":"Rizkallah","year":"2017","journal-title":"Crit. Rev. Oncog."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5826741","DOI":"10.1155\/2022\/5826741","article-title":"A Systematic Pan-Cancer Analysis of YY1 Aberrations and their Relationship with Clinical Outcome, Tumor Microenvironment, and Therapeutic Targets","volume":"2022","author":"Fu","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1615\/CritRevOncog.2017021071","article-title":"The role of transcription factor YY1 in the biology of cancer","volume":"22","author":"Agarwal","year":"2017","journal-title":"Crit. Rev. Oncog."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4062","DOI":"10.1073\/pnas.1503696112","article-title":"Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas","volume":"112","author":"Cromer","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1158\/0008-5472.CAN-16-1099","article-title":"GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis","volume":"76","author":"Agarwal","year":"2016","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1016\/j.ajpath.2012.01.037","article-title":"Yin Yang 1 plays an essential role in breast cancer and negatively regulates p27","volume":"180","author":"Wan","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1038\/onc.2012.360","article-title":"A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma","volume":"32","author":"Yang","year":"2013","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1479-5876-12-80","article-title":"Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma","volume":"12","author":"Kang","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"692405","DOI":"10.3389\/fonc.2021.692405","article-title":"YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression through Impairment of GAS5-Mediated p53 Stability","volume":"11","author":"Wei","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1093\/nar\/gkab252","article-title":"Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2\/4-PFKP during tumorigenesis of advanced prostate cancer","volume":"49","author":"Xu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1186\/bcr1851","article-title":"The combined immunodetection of AP-2alpha and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors","volume":"10","author":"Allouche","year":"2008","journal-title":"Breast Cancer Res. BCR"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e31990","DOI":"10.1097\/MD.0000000000031990","article-title":"Crosstalk between YY1 and lncRNAs in cancer: A review","volume":"101","author":"Wang","year":"2022","journal-title":"Medicine"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"D\u2019Aguanno, S., and Del Bufalo, D. (2020). Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer. Cells, 9.","DOI":"10.3390\/cells9051287"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1111\/febs.13624","article-title":"The Deadly Landscape of Pro-Apoptotic BCL-2 Proteins in the Outer Mitochondrial Membrane","volume":"283","author":"Chipuk","year":"2016","journal-title":"FEBS J."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Roufayel, R., Younes, K., Al-Sabi, A., and Murshid, N. (2022). BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis. Life, 12.","DOI":"10.3390\/life12020256"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"985363","DOI":"10.3389\/fonc.2022.985363","article-title":"The role of bcl-2 family proteins in regulating apoptosis and cancer therapy","volume":"12","author":"Qian","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1080\/10428194.2017.1283032","article-title":"Pathways and mechanisms of venetoclax resistance","volume":"58","author":"Bose","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cetraro, P., Plaza-Diaz, J., MacKenzie, A., and Abad\u00eda-Molina, F. (2022). A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer. Cancers, 14.","DOI":"10.3390\/cancers14071671"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/med.21547","article-title":"Therapeutic strategies involving survivin inhibition in cancer","volume":"39","author":"Quesada","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"314","DOI":"10.7150\/jca.13332","article-title":"Survivin and Tumorigenesis: Molecular Mechanisms and Therapeutic Strategies","volume":"7","author":"Chen","year":"2016","journal-title":"J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Bui, I., Baritaki, S., Libra, M., Zaravinos, A., and Bonavida, B. (2023). Cancer resistance is mediated by the upregulation of several anti-apoptotic gene products via the inducible nitric oxide synthase\/nitric oxide pathway: Therapeutic implications. Antioxid. Redox Signal.","DOI":"10.1089\/ars.2023.0250"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"603","DOI":"10.18632\/aging.100934","article-title":"Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies","volume":"8","author":"Pistritto","year":"2016","journal-title":"Aging"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cui, J., and Placzek, W.J. (2018). Post-Transcriptional Regulation of Anti-Apoptotic BCL2 Family Members. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010308"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1046\/j.1365-2443.1998.00223.x","article-title":"Role of Bcl-2 family proteins in apoptosis: Apoptosomes or mitochondria?","volume":"3","author":"Tsujimoto","year":"1998","journal-title":"Genes Cells"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1182\/blood-2014-04-571786","article-title":"BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma","volume":"125","author":"Correia","year":"2015","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1158\/1541-7786.MCR-07-0088","article-title":"Modulation of bcl-xL in tumor cells regulates angiogenesis through CXCL8 expression","volume":"5","author":"Giorgini","year":"2007","journal-title":"Mol. Cancer Res. MCR"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1038\/s41419-017-0055-y","article-title":"BCL-XL overexpression promotes tumor progression-associated properties","volume":"8","author":"Trisciuoglio","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.18632\/oncotarget.6405","article-title":"Bcl-2 family proteins as regulators of cancer cell invasion and metastasis: A review focusing on mitochondrial respiration and reactive oxygen species","volume":"7","author":"Um","year":"2015","journal-title":"Oncotarget"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13045-021-01079-1","article-title":"Targeting MCL-1 in cancer: Current status and perspectives","volume":"14","author":"Wang","year":"2021","journal-title":"J. Hematol. Oncol. J. Hematol. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4910","DOI":"10.1158\/1078-0432.CCR-21-0464","article-title":"Pharmacologic targeting of Mcl-1 induces mitochondrial dysfunction and apoptosis in B-cell lymphoma cells in a TP53- and BAX-dependent manner","volume":"27","author":"Liu","year":"2021","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"521","DOI":"10.4049\/jimmunol.181.1.521","article-title":"The Anti-apoptotic Bcl-2 Family Member Mcl-1 Promotes T Lymphocyte Survival at Multiple Stages","volume":"181","author":"Dzhagalov","year":"2008","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"23296","DOI":"10.1074\/jbc.M111.237586","article-title":"Survivin Monomer Plays an Essential Role in Apoptosis Regulation","volume":"286","author":"Pavlyukov","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12929-020-0627-5","article-title":"Anti-apoptotic proteins in the autophagic world: An update on functions of XIAP, Survivin, and BRUCE","volume":"27","author":"Cheung","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4103\/0971-5916.159250","article-title":"Survivin: A molecular biomarker in cancer","volume":"141","author":"Jaiswal","year":"2015","journal-title":"Indian J. Med. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1158\/0008-5472.CAN-04-4284","article-title":"A survivin gene signature predicts aggressive tumor behavior","volume":"65","author":"Salz","year":"2005","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1182\/blood.V116.21.2887.2887","article-title":"The Pivotal Role of Yin Yang 1 (YY1) Inhibition (and downstream Bcl-2\/Bclxl) by Galiximab (anti-CD80 mAb) In the Reversal of Resistance of B-NHL Cells to Chemotherapy","volume":"116","author":"Vega","year":"2010","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13046-017-0535-z","article-title":"Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma","volume":"36","author":"Shvartsur","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_82","unstructured":"\u00d6zenver, N., and Efferth, T. (2020). Prognostic and Therapeutic Applications of RKIP in Cancer, Academic Press."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1615\/CritRevImmunol.v29.i3.40","article-title":"The activated NF-kappaB-Snail-RKIP circuitry in cancer regulates both the metastatic cascade and resistance to apoptosis by cytotoxic drugs","volume":"29","author":"Wu","year":"2009","journal-title":"Crit. Rev. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Guan, H., Zhang, W., Liu, H., Jiang, Y., Li, F., Wu, M., Waterhouse, G.I.N., Sun-Waterhouse, D., and Li, D. (2023). Quercetin Induces Apoptosis in HepG2 Cells via Directly Interacting with YY1 to Disrupt YY1-p53 Interaction. Metabolites, 13.","DOI":"10.3390\/metabo13020229"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1158\/1535-7163.MCT-11-0635","article-title":"Galiximab Signals B-NHL Cells and Inhibits the Activities of NF-\u03baB\u2013Induced YY1- and Snail-Resistant Factors: Mechanism of Sensitization to Apoptosis by Chemoimmunotherapeutic Drugs","volume":"11","author":"Vega","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Vivarelli, S., Falzone, L., Candido, S., Bonavida, B., and Libra, M. (2021). YY1 Silencing Induces 5-Fluorouracil-Resistance and BCL2L15 Downregulation in Colorectal Cancer Cells: Diagnostic and Prognostic Relevance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168481"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1128\/MCB.06466-11","article-title":"Phosphorylation of the Transcription Factor YY1 by CK2\u03b1 Prevents Cleavage by Caspase 7 during Apoptosis","volume":"32","author":"Riman","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1111\/exd.14628","article-title":"Transcription factor YY1 contributes to human melanoma cell growth through modulating the p53 signalling pathway","volume":"31","author":"Zhou","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_89","first-page":"1926","article-title":"Mir-218 inhibits the proliferation of human glioma cells through downregulation of Yin Yang 1","volume":"17","author":"Gao","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.cell.2004.06.004","article-title":"Yin Yang 1 is a negative regulator of p53","volume":"117","author":"Sui","year":"2004","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-023-01347-1","article-title":"Targeting p53 pathways: Mechanisms, structures, and advances in therapy","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Morales-Mart\u00ednez, M., and Vega, M.I. (2022). Roles and Regulation of BCL-xL in Hematological Malignancies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042193"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1158\/0008-5472.CAN-12-0366","article-title":"Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1\u03b1 in a p53-Independent Manner","volume":"73","author":"Wu","year":"2013","journal-title":"Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/jor.21193","article-title":"Increased levels of hypoxia-inducible factor-1\u03b1 are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma","volume":"29","author":"Chen","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10004","DOI":"10.1074\/jbc.M805997200","article-title":"BCL-xL is a target gene regulated by hypoxia-inducible factor-1\u03b1","volume":"284","author":"Chen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3109\/10428194.2012.733874","article-title":"Hypoxia inducible factor-1\u03b1 induces chemoresistance phenotype in non-Hodgkin lymphoma cell line via up-regulation of Bcl-xL","volume":"54","author":"Vega","year":"2013","journal-title":"Leuk. Lymphoma"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.18632\/oncotarget.26745","article-title":"Regulation of Kr\u00fcppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma","volume":"10","author":"Vega","year":"2019","journal-title":"Oncotarget"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s12192-010-0199-5","article-title":"KLF4 promotes hydrogen-peroxide-induced apoptosis of chronic myeloid leukemia cells involving the bcl-2\/bax pathway","volume":"15","author":"Li","year":"2010","journal-title":"Cell Stress Chaperones"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.molonc.2012.12.002","article-title":"KLF4 overexpression and apigenin treatment down regulated anti-apoptotic Bcl-2 proteins and matrix metalloproteinases to control growth of human malignant neuroblastoma SK-N-DZ and IMR-32 cells","volume":"7","author":"Mohan","year":"2013","journal-title":"Mol. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e1699","DOI":"10.1038\/cddis.2015.65","article-title":"Regulation of anti-apoptotic signaling by Kruppel-like factors 4 and 5 mediates lapatinib resistance in breast cancer","volume":"6","author":"Farrugia","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.jhep.2009.12.024","article-title":"The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma","volume":"52","author":"Shimizu","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Lucian\u00f2, A.M., P\u00e9rez-Oliva, A.B., Mulero, V., and Del Bufalo, D. (2021). Bcl-xL: A Focus on Melanoma Pathobiology. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052777"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1038\/s41418-020-00692-w","article-title":"Regulation of Bcl-XL by non-canonical NF-\u03baB in the context of CD40-induced drug resistance in CLL","volume":"28","author":"Haselager","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.4049\/jimmunol.175.4.2174","article-title":"Rituximab-Induced Inhibition of YY1 and Bcl-xL Expression in Ramos Non-Hodgkin\u2019s Lymphoma Cell Line via Inhibition of NF-\u03baB Activity: Role of YY1 and Bcl-xL in Fas Resistance and Chemoresistance, Respectively1","volume":"175","author":"Vega","year":"2005","journal-title":"J Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13045-020-01007-9","article-title":"MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents","volume":"13","author":"Bolomsky","year":"2020","journal-title":"J. Hematol. Oncol. J. Hematol. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"11177","DOI":"10.1002\/cam4.5745","article-title":"The role of transcription factor Yin Yang-1 in colorectal cancer","volume":"12","author":"Shao","year":"2023","journal-title":"Cancer Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.4161\/cc.10.16.16952","article-title":"Mcl-1 and YY1 inhibition and induction of DR5 by the BH3-mimetic Obatoclax (GX15-070) contribute in the sensitization of B-NHL cells to TRAIL apoptosis","volume":"10","author":"Baritaki","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Morales-Martinez, M., and Vega, M.I. (2021). Participation of different mirnas in the regulation of YY1: Their role in pathogenesis, chemoresistance, and therapeutic implication in hematologic malignancies. YY1 Control. Pathog. Drug Resist. Cancer, 171\u2013198.","DOI":"10.1016\/B978-0-12-821909-6.00010-9"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Vivarelli, S., Falzone, L., Ligresti, G., Candido, S., Garozzo, A., Magro, G.G., Bonavida, B., and Libra, M. (2020). Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176446"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"jcs223826","DOI":"10.1242\/jcs.223826","article-title":"Survivin at a glance","volume":"132","author":"Wheatley","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbrc.2014.01.169","article-title":"Yin Yang 1 regulates the transcriptional repression of survivin","volume":"445","author":"Galloway","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1615\/CritRevOncog.2017020836","article-title":"Yin Yang 1 (YY1): Regulation of Survivin and Its Role In Invasion and Metastasis","volume":"22","author":"Galloway","year":"2017","journal-title":"Crit. Rev. Oncog."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1128\/MCB.26.9.3565-3581.2006","article-title":"Essential dosage-dependent functions of the transcription factor yin yang 1 in late embryonic development and cell cycle progression","volume":"26","author":"Affar","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1038\/onc.2012.526","article-title":"microRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis","volume":"32","author":"Zhang","year":"2013","journal-title":"Oncogene"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.isci.2018.03.009","article-title":"YY1 Upregulates Checkpoint Receptors and Downregulates Type I Cytokines in Exhausted, Chronically Stimulated Human T Cells","volume":"2","author":"Balkhi","year":"2018","journal-title":"iScience"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.3389\/fimmu.2019.01719","article-title":"T Cell Dysfunction in Cancer Immunity and Immunotherapy","volume":"10","author":"Xia","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.pharmthera.2015.01.011","article-title":"Prognostic significance of YY1 protein expression and mRNA levels by bioinformatics analysis in human cancers: A therapeutic target","volume":"150","author":"Bonavida","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4993","DOI":"10.1038\/sj.onc.1207655","article-title":"Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-\u03baB and inhibition of Bcl-xL expression","volume":"23","author":"Vega","year":"2004","journal-title":"Oncogene"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1182\/blood.V126.23.1466.1466","article-title":"KLF4 and YY1 Are Resistant Factors in NHL and Potential Therapeutic Targets: The New Resistant NF-\u03bab\/YY1\/KLF4\/BclxL\/Mcl-1 Axis","volume":"126","author":"Vega","year":"2015","journal-title":"Blood"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1158\/1078-0432.CCR-20-2188","article-title":"Bone Marrow Mesenchymal Stromal Cells Can Render Multiple Myeloma Cells Resistant to Cytotoxic Machinery of CAR T Cells through Inhibition of Apoptosis","volume":"27","author":"Holthof","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1615\/CritRevOncog.2017020472","article-title":"Therapeutic YY1 inhibitors in cancer: All in one","volume":"22","author":"Bonavida","year":"2017","journal-title":"Crit. Rev. Oncog."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.3892\/mmr.2015.3324","article-title":"MicroRNA-181 targets Yin Yang 1 expression and inhibits cervical cancer progression","volume":"11","author":"Zhou","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Hafezi, S., and Rahmani, M. (2021). Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives. Cancers, 13.","DOI":"10.3390\/cancers13061292"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/s41419-020-03144-y","article-title":"Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance","volume":"11","author":"Kapoor","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"114184","DOI":"10.1016\/j.ejmech.2022.114184","article-title":"Trends in targeting Bcl-2 anti-apoptotic proteins for cancer treatment","volume":"232","author":"Zhang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1038\/s41591-019-0668-z","article-title":"A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity","volume":"25","author":"Khan","year":"2019","journal-title":"Nat. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/s41467-021-21573-x","article-title":"Proteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells","volume":"12","author":"Kolb","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"112186","DOI":"10.1016\/j.ejmech.2020.112186","article-title":"Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity","volume":"192","author":"Zhang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"8152","DOI":"10.1021\/acs.jmedchem.9b00919","article-title":"Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1\/Bcl-2 Derived from Nonselective Target Binding Ligands","volume":"62","author":"Wang","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/17460441.2022.2077329","article-title":"Advances in nanotechnology-based platforms for survivin-targeted drug discovery","volume":"17","author":"George","year":"2022","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1186\/s13046-019-1362-1","article-title":"Cancer therapeutics using survivin BIRC5 as a target: What can we do after over two decades of study?","volume":"38","author":"Li","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1158\/0008-5472.CAN-15-1874","article-title":"Effective Targeting of the Survivin Dimerization Interface with Small-Molecule Inhibitors","volume":"76","author":"Qi","year":"2016","journal-title":"Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4267\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:39:14Z","timestamp":1760128754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,25]]},"references-count":132,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cancers15174267"],"URL":"https:\/\/doi.org\/10.3390\/cancers15174267","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,25]]}}}