{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T18:10:20Z","timestamp":1778523020638,"version":"3.51.4"},"reference-count":96,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nuclear factor kappa B (NF-\u03baB) signaling plays a central role in inflammation, immunity, cell survival, and cancer progression. Its constitutive activation is frequently observed in breast cancer, contributing to tumor growth, treatment resistance, and metastasis. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may modulate NF-\u03baB signaling in a subtype-specific or -independent manner. The aim of the study was to identify miRNAs that may potentially regulate the activity of genes associated with NF-\u03baB signaling across five molecular subtypes of breast cancer in Polish women. Tumor and matched normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC, n = 43). Expression profile of selected NF-\u03baB-related genes were evaluated using mRNA microarrays and RT-qPCR. Protein levels were assessed by ELISA. Candidate regulatory miRNAs were identified via miRNA microarrays and validated using the miRDB database. A consistent upregulation of MAP3K7, TAB2, TNFAIP3, CSNK2A1, BCL2L1, XIAP, CXCL2, and PLAU was observed across all subtypes, suggesting activation of canonical NF-\u03baB signaling. Downregulation of specific miRNAs, miR-1297 and miR-30a (targeting MAP3K7), miR-134 (TAB2), miR-125b (TNFAIP3), and miR-4329 (XIAP), may contribute to this deregulation. For CSNK2A1, BCL2L1, CXCL2, and PLAU, no regulatory miRNAs meeting our criteria were identified. Our study reveals a subtype-independent activation of the canonical NF-\u03baB signaling pathway in breast cancer, underpinned by consistent upregulation of key components (at both the transcript and protein levels. Dysregulation of specific miRNAs likely contributes to this altered gene expression. These findings suggest the presence of a common NF-\u03baB-driven oncogenic program across molecular subtypes, with potential implications for developing miRNA-based therapeutic strategies targeting inflammation, survival signaling, and treatment resistance in breast cancer.<\/jats:p>","DOI":"10.3390\/ijms27094055","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:50:01Z","timestamp":1777618201000},"page":"4055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subtype-Independent Activation of NF-\u03baB Signaling in Breast Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"El\u017cbieta","family":"Mitka-Krysiak","sequence":"first","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kr\u00f3l-Jatr\u0119ga","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Ossowski","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-6167","authenticated-orcid":false,"given":"Nikola","family":"Zmarz\u0142y","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Bereza","sequence":"additional","affiliation":[{"name":"Department of Mother and Child Health, Faculty of Health Sciences, Institute of Nursing and Midwifery, Jagiellonian University Medical College, 31-008 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Ordon","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Sirek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"},{"name":"Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, 40-555 Katowice, Poland"},{"name":"Department of Plastic and Reconstructive Surgery, Hospital for Minimally Invasive and Reconstructive Surgery in Bielsko-Bia\u0142a, 43-316 Bielsko-Biala, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Sirek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kacper","family":"Boro\u0144","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, 40-555 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-5829","authenticated-orcid":false,"given":"Dariusz","family":"Boro\u0144","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"},{"name":"Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University in Krak\u00f3w, 30-705 Krak\u00f3w, Poland"},{"name":"Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, 40-055 Katowice, Poland"},{"name":"Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, 31-826 Krak\u00f3w, Poland"},{"name":"Faculty of Medicine, VIZJA University, 01-043 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Wyrobiec","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Szczepanik","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Skorek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-7145","authenticated-orcid":false,"given":"Beniamin Oskar","family":"Grabarek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"(2025, April 01). Available online: https:\/\/onkologia.org.pl\/sites\/default\/files\/publications\/2024-01\/0_krn-2023-book-2024-01-22.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41420-023-01650-4","article-title":"A Primary Luminal\/HER2 Negative Breast Cancer Patient with Mismatch Repair Deficiency","volume":"9","author":"Yang","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"\u0141ukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., and Stanis\u0142awek, A. (2021). Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies\u2014An Updated Review. Cancers, 13.","DOI":"10.3390\/cancers13174287"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41523-023-00554-x","article-title":"Rare Subtypes of Triple Negative Breast Cancer: Current Understanding and Future Directions","volume":"9","author":"Thomas","year":"2023","journal-title":"npj Breast Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/mco2.104","article-title":"NF-\u03baB Signaling in Inflammation and Cancer","volume":"2","author":"Zhang","year":"2021","journal-title":"MedComm"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in Biology and Targeted Therapy: New Insights and Translational Implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-\u03baB in Inflammation and Cancer","volume":"22","author":"Mao","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12964-023-01207-z","article-title":"NF-\u03baB Signaling in Neoplastic Transition from Epithelial to Mesenchymal Phenotype","volume":"21","author":"Oh","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wu, X., Sun, L., and Xu, F. (2023). NF-\u03baB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances. Pharmaceuticals, 16.","DOI":"10.3390\/ph16060783"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122684","DOI":"10.1016\/j.lfs.2024.122684","article-title":"NF-\u03baB Signaling in Therapy Resistance of Breast Cancer: Mechanisms, Approaches, and Challenges","volume":"348","author":"Guo","year":"2024","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cao, Y., Yi, Y., Han, C., and Shi, B. (2024). NF-\u03baB Signaling Pathway in Tumor Microenvironment. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1476030"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102103","DOI":"10.1016\/j.ceb.2022.102103","article-title":"Encoding and Decoding NF-\u03baB Nuclear Dynamics","volume":"77","author":"Wibisana","year":"2022","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bacher, S., Meier-Soelch, J., Kracht, M., and Schmitz, M.L. (2021). Regulation of Transcription Factor NF-\u03baB in Its Natural Habitat: The Nucleus. Cells, 10.","DOI":"10.3390\/cells10040753"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Prezioso, C., Limongi, D., Checconi, P., Ciotti, M., Legramante, J.M., Petrangeli, C.M., Leonardis, F., Giovannelli, A., Terrinoni, A., and Bernardini, S. (2024). Role of miR-9 in Modulating NF-\u03baB Signaling and Cytokine Expression in COVID-19 Patients. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168930"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3344\/kjp.24386","article-title":"MiR-298 Suppresses Astrocytic NF-\u03baB Activity and Neuroinflammation via Targeting MyD88 in Bone Cancer Pain","volume":"38","author":"Liu","year":"2025","journal-title":"Korean J. Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3724\/abbs.2025038","article-title":"miR-32-5p Suppresses the Progression of Hepatocellular Carcinoma by Regulating the GSK3\u03b2\/NF-\u03baB Signaling","volume":"57","author":"Wang","year":"2025","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.1007\/s00277-024-06062-7","article-title":"MiR-525-5p Modulates Cell Proliferation, Cell Cycle, and Apoptosis in Burkitt\u2019s Lymphoma by Targeting MyD88 and Regulating the NF-\u03baB Signaling Pathway","volume":"103","author":"Chen","year":"2024","journal-title":"Ann. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11784","DOI":"10.1007\/s12035-025-04949-8","article-title":"MicroRNA-3135b as a Therapeutic Target and Clinical Biomarker for Stroke: Regulation of the NF-\u03baB\/IKK\u03b2 Signaling Pathway","volume":"62","author":"Liu","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3892\/etm.2021.10201","article-title":"Cascades between miRNAs, lncRNAs and the NF-\u03baB Signaling Pathway in Gastric Cancer (Review)","volume":"22","author":"Chen","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108810","DOI":"10.1016\/j.pharmthera.2025.108810","article-title":"Targeting TAK1: Evolution of Inhibitors, Challenges, and Future Directions","volume":"267","author":"Benedik","year":"2025","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Iacobazzi, D., Convertini, P., Todisco, S., Santarsiero, A., Iacobazzi, V., and Infantino, V. (2023). New Insights into NF-\u03baB Signaling in Innate Immunity: Focus on Immunometabolic Crosstalks. Biology, 12.","DOI":"10.3390\/biology12060776"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1158\/1078-0432.CCR-24-1004","article-title":"TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma","volume":"30","author":"Sheng","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/s41419-022-05335-1","article-title":"HDAC6-Dependent Deacetylation of TAK1 Enhances sIL-6R Release to Promote Macrophage M2 Polarization in Colon Cancer","volume":"13","author":"Xu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7549","DOI":"10.18632\/oncotarget.2273","article-title":"Elevated TAK1 Augments Tumor Growth and Metastatic Capacities of Ovarian Cancer Cells through Activation of NF-\u03baB Signaling","volume":"5","author":"Cai","year":"2014","journal-title":"Oncotarget"},{"key":"ref_26","first-page":"14449","article-title":"The Role of TAK1 Expression in Thyroid Cancer","volume":"8","author":"Lin","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.athoracsur.2012.09.050","article-title":"Positive Transforming Growth Factor-\u03b2 Activated Kinase-1 Expression Has an Unfavorable Impact on Survival in T3N1-3M0 Esophageal Squamous Cell Carcinomas","volume":"95","author":"Wen","year":"2013","journal-title":"Ann. Thorac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.3892\/mmr.2017.6998","article-title":"Expression and Function of Transforming Growth Factor-\u03b2-Activated Protein Kinase 1 in Gastric Cancer","volume":"16","author":"Yang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"995","DOI":"10.18632\/oncotarget.2739","article-title":"Targeting of TGF-\u03b2-Activated Protein Kinase 1 Inhibits Chemokine (C-C Motif) Receptor 7 Expression, Tumor Growth and Metastasis in Breast Cancer","volume":"6","author":"Huang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41420-023-01419-9","article-title":"Suppression of Triple-Negative Breast Cancer Aggressiveness by LGALS3BP via Inhibition of the TNF-\u03b1\u2013TAK1\u2013MMP9 Axis","volume":"9","author":"Sun","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_31","first-page":"1314","article-title":"Hsa_circ_0091074 Regulates TAZ Expression via microRNA-1297 in Triple Negative Breast Cancer Cells","volume":"56","author":"Hu","year":"2020","journal-title":"Int. J. Oncol."},{"key":"ref_32","first-page":"1045","article-title":"Differential Expression of miR-1297, miR-3191-5p, miR-4435, and miR-4465 in Malignant and Benign Breast Tumors","volume":"23","author":"Mosapour","year":"2020","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3892\/ol.2020.12140","article-title":"MicroRNA-1297 Downregulation Inhibits Breast Cancer Cell Epithelial-Mesenchymal Transition and Proliferation in a FA2H-Dependent Manner","volume":"20","author":"Li","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cheng, C.-W., Liu, Y.-F., Liao, W.-L., Chen, P.-M., Hung, Y.-T., Lee, H.-J., Cheng, Y.-C., Wu, P.-E., Lu, Y.-S., and Shen, C.-Y. (2024). miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1\u03b1 to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells. Cancers, 16.","DOI":"10.3390\/cancers16030657"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3892\/ijmm.2017.3084","article-title":"miR-30a Inhibits the Biological Function of Breast Cancer Cells by Targeting Notch1","volume":"40","author":"Zhang","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_36","first-page":"406","article-title":"miR-30a Regulates the Proliferation and Invasion of Breast Cancer Cells by Targeting Snail","volume":"17","author":"Xiao","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5053","DOI":"10.7150\/jca.57752","article-title":"miR-30a\/SOX4 Double Negative Feedback Loop Is Modulated by Disulfiram and Regulates EMT and Stem Cell-like Properties in Breast Cancer","volume":"12","author":"Liu","year":"2021","journal-title":"J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s00018-025-05631-x","article-title":"Role of TLRs as Signaling Cascades to Combat Infectious Diseases: A Review","volume":"82","author":"Salauddin","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.1038\/onc.2011.627","article-title":"Targeting of the Adaptor Protein Tab2 as a Novel Approach to Revert Tamoxifen Resistance in Breast Cancer Cells","volume":"31","author":"Cutrupi","year":"2012","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13058-015-0591-2","article-title":"Identification of Two Novel Mammographic Density Loci at 6Q25.1","volume":"17","author":"Brand","year":"2015","journal-title":"Breast Cancer Res."},{"key":"ref_41","first-page":"14472","article-title":"C\/EBP\u03b1 Inhibits Proliferation of Breast Cancer Cells via a Novel Pathway of miR-134\/CREB","volume":"8","author":"Zhang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"32774","DOI":"10.18632\/oncotarget.5192","article-title":"miR-134 in Extracellular Vesicles Reduces Triple-Negative Breast Cancer Aggression and Increases Drug Sensitivity","volume":"6","author":"Lowry","year":"2015","journal-title":"Oncotarget"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.3892\/ol.2017.5644","article-title":"MicroRNA-134 Targets KRAS to Suppress Breast Cancer Cell Proliferation, Migration and Invasion","volume":"13","author":"Su","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"739","DOI":"10.21873\/anticanres.14825","article-title":"Immunohistochemical Assessment of TNFAIP3\/A20 Expression Correlates with Early Tumorigenesis in Breast Cancer","volume":"41","author":"Talaat","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1038\/sj.onc.1210269","article-title":"A20\/TNFAIP3, a New Estrogen-Regulated Gene That Confers Tamoxifen Resistance in Breast Cancer Cells","volume":"26","author":"Vendrell","year":"2007","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41388-018-0472-0","article-title":"The Pleiotropic Effects of TNF\u03b1 in Breast Cancer Subtypes Is Regulated by TNFAIP3\/A20","volume":"38","author":"Lee","year":"2019","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"681","DOI":"10.21873\/anticanres.15527","article-title":"The A20\/TNFAIP3-CDC20-CASP1 Axis Promotes Inflammation-Mediated Metastatic Disease in Triple-Negative Breast Cancer","volume":"42","author":"Song","year":"2022","journal-title":"Anticancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Jeon, H., and Lee, C. (2025). The Dual Role of A20 (TNFAIP3) in Viral Infection: A Context-Dependent Regulator of Immunity and Pathogenesis. Viruses, 17.","DOI":"10.3390\/v17121634"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/cmi.2011.59","article-title":"Regulation of NF-\u03baB Signaling by the A20 Deubiquitinase","volume":"9","author":"Shembade","year":"2012","journal-title":"Cell. Mol. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB Pathway for the Therapy of Diseases: Mechanism and Clinical Study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Courtois, G., and Fauvarque, M.-O. (2018). The Many Roles of Ubiquitin in NF-\u03baB Signaling. Biomedicines, 6, Erratum in Oncogene\u00a02019, 38, 5749. https:\/\/doi.org\/10.1038\/s41388-019-0838-y.","DOI":"10.3390\/biomedicines6020043"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1042\/BCJ20210139","article-title":"Inhibitory Feedback Control of NF-\u03baB Signalling in Health and Disease","volume":"478","author":"Prescott","year":"2021","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tang, F., Zhang, R., He, Y., Zou, M., Guo, L., and Xi, T. (2012). MicroRNA-125b Induces Metastasis by Targeting STARD13 in MCF-7 and MDA-MB-231 Breast Cancer Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035435"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1158\/0008-5472.CAN-10-2435","article-title":"miR-125b Is Methylated and Functions as a Tumor Suppressor by Regulating the ETS1 Proto-Oncogene in Human Invasive Breast Cancer","volume":"71","author":"Zhang","year":"2011","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Feliciano, A., Castellvi, J., Artero-Castro, A., Leal, J.A., Romagosa, C., Hern\u00e1ndez-Losa, J., Peg, V., Fabra, A., Vidal, F., and Kondoh, H. (2013). miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-\u03b1, CCNJ, and MEGF9. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076247"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1177\/1947601909357933","article-title":"Mucin 1 Oncoprotein Expression Is Suppressed by the miR-125b Oncomir","volume":"1","author":"Rajabi","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_57","first-page":"2639","article-title":"miR-125b Inhibited Epithelial\u2013Mesenchymal Transition of Triple-Negative Breast Cancer by Targeting MAP2K7","volume":"9","author":"Hong","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Halloran, D., Pandit, V., and Nohe, A. (2022). The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review. J. Dev. Biol., 10.","DOI":"10.3390\/jdb10030031"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1016\/j.ajpath.2016.08.007","article-title":"CK2\u03b1\/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients","volume":"186","author":"Bae","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6484","DOI":"10.18632\/oncotarget.2248","article-title":"Therapeutic CK2 Inhibition Attenuates Diverse Prosurvival Signaling Cascades and Decreases Cell Viability in Human Breast Cancer Cells","volume":"5","author":"Gray","year":"2014","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Song, J., and Bae, Y.-S. (2021). CK2 Down-Regulation Increases the Expression of Senescence-Associated Secretory Phenotype Factors through NF-\u03baB Activation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010406"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11778","DOI":"10.18632\/oncotarget.2634","article-title":"Bcl-xL Mediates Therapeutic Resistance of a Mesenchymal Breast Cancer Cell Subpopulation","volume":"5","author":"Keitel","year":"2014","journal-title":"Oncotarget"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41392-025-02176-0","article-title":"The BCL2 Family: From Apoptosis Mechanisms to New Advances in Targeted Therapy","volume":"10","author":"Vogler","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e202302353","DOI":"10.26508\/lsa.202302353","article-title":"Genome-Wide CRISPR Screen Reveals the Synthetic Lethality between BCL2L1 Inhibition and Radiotherapy","volume":"7","author":"Yin","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kawiak, A., and Kostecka, A. (2022). Regulation of Bcl-2 Family Proteins in Estrogen Receptor-Positive Breast Cancer and Their Implications in Endocrine Therapy. Cancers, 14.","DOI":"10.3390\/cancers14020279"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14177","DOI":"10.1038\/s41598-024-64696-z","article-title":"Low BCL-xL Expression in Triple-Negative Breast Cancer Cells Favors Chemotherapy Efficacy, and This Effect Is Limited by Cancer-Associated Fibroblasts","volume":"14","author":"Nocquet","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Alcon, C., Za\u00f1udo, J.G.T., Albert, R., Wagle, N., Scaltriti, M., Letai, A., Samitier, J., and Montero, J. (2021). ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins. Cells, 10.","DOI":"10.3390\/cells10071659"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Tu, H., and Costa, M. (2020). XIAP\u2019s Profile in Human Cancer. Biomolecules, 10.","DOI":"10.3390\/biom10111493"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Devi, G.R., Finetti, P., Morse, M.A., Lee, S., de Nonneville, A., Van Laere, S., Troy, J., Geradts, J., McCall, S., and Bertucci, F. (2021). Expression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Breast Cancer Is Associated with Shorter Survival and Resistance to Chemotherapy. Cancers, 13.","DOI":"10.3390\/cancers13112807"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hussain, A.R., Siraj, A.K., Ahmed, M., Bu, R., Pratheeshkumar, P., Alrashed, A.M., Qadri, Z., Ajarim, D., Al-Dayel, F., and Beg, S. (2017). XIAP Over-Expression Is an Independent Poor Prognostic Marker in Middle Eastern Breast Cancer and Can Be Targeted to Induce Efficient Apoptosis. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3627-4"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1159\/000488273","article-title":"Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A\/MiR-532-3p\/HK2 Pathway in Ovarian Cancer Cells","volume":"45","author":"Zhou","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Czop, M., Gasi\u0144ska, K., Kosior-Jarecka, E., Wr\u00f3bel-Dudzi\u0144ska, D., Kocki, J., and \u017barnowski, T. (2023). Twenty Novel MicroRNAs in the Aqueous Humor of Pseudoexfoliation Glaucoma Patients. Cells, 12.","DOI":"10.3390\/cells12050737"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1111\/jocs.15868","article-title":"miR-6718-5p and miR-4329 Can Be Used as Potential Biomarkers for Acute Myocardial Infarction","volume":"36","author":"Chen","year":"2021","journal-title":"J. Card. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12935-025-03765-3","article-title":"CXCL2: A Key Player in the Tumor Microenvironment and Inflammatory Diseases","volume":"25","author":"Lv","year":"2025","journal-title":"Cancer Cell Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.canlet.2017.09.030","article-title":"CXCR2 Promotes Breast Cancer Metastasis and Chemoresistance via Suppression of AKT1 and Activation of COX2","volume":"412","author":"Xu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"SenGupta, S., Hein, L.E., Xu, Y., Zhang, J., Konwerski, J.R., Li, Y., Johnson, C., Cai, D., Smith, J.L., and Parent, C.A. (2021). Triple-Negative Breast Cancer Cells Recruit Neutrophils by Secreting TGF-\u03b2 and CXCR2 Ligands. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.659996"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wang, F., Yuan, C., Wu, H.-Z., Liu, B., and Yang, Y.-F. (2021). Bioinformatics, Molecular Docking and Experiments In Vitro Analyze the Prognostic Value of CXC Chemokines in Breast Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.665080"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"102779","DOI":"10.1016\/j.jbc.2022.102779","article-title":"Proteomics Analysis Uncovers Plasminogen Activator PLAU as a Target of the STING Pathway for Suppression of Cancer Cell Migration and Invasion","volume":"299","author":"Tan","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Sarno, F., Goubert, D., Logie, E., Rutten, M.G.S., Koncz, M., Deben, C., Niemarkt, A.E., Altucci, L., Verschure, P.J., and Kiss, A. (2022). Functional Validation of the Putative Oncogenic Activity of PLAU. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010102"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e1043","DOI":"10.1038\/cddis.2014.5","article-title":"Plasminogen Activator Urokinase Expression Reveals TRAIL Responsiveness and Supports Fractional Survival of Cancer Cells","volume":"5","author":"Pavet","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"166965","DOI":"10.1016\/j.bbadis.2023.166965","article-title":"Pan-Cancer Analysis of PLAU Indicates Its Potential Prognostic Value and Correlation with Neutrophil Infiltration in BLCA","volume":"1870","author":"Shi","year":"2024","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_82","unstructured":"Biswas, S., and Menon, L. (2021). miRNA-Based Therapeutic Strategies. RNA-Based Mechanisms in Cancer, World Scientific."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Huang, Q., Yu, L., Zhu, D., Li, Y., Xue, Z., Hua, Z., Luo, X., Song, Z., and Lu, C. (2022). The Role of miRNA in Tumor Immune Escape and miRNA-Based Therapeutic Strategies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.807895"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Pagoni, M., Cava, C., Sideris, D.C., Avgeris, M., Zoumpourlis, V., Michalopoulos, I., and Drakoulis, N. (2023). miRNA-Based Technologies in Cancer Therapy. J. Pers. Med., 13.","DOI":"10.3390\/jpm13111586"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA Therapeutics: Towards a New Era for the Management of Cancer and Other Diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.omtn.2017.06.005","article-title":"Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine","volume":"8","author":"Chakraborty","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10637-016-0407-y","article-title":"Phase I Study of MRX34, a Liposomal miR-34a Mimic, Administered Twice Weekly in Patients with Advanced Solid Tumors","volume":"35","author":"Beg","year":"2017","journal-title":"Investig. New Drugs"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41573-019-0017-4","article-title":"The Current State and Future Directions of RNAi-Based Therapeutics","volume":"18","author":"Setten","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sirek, T., Borawski, P., Kr\u00f3l-Jatr\u0119ga, K., Sirek, A., Zmarz\u0142y, N., Boro\u0144, D., Chalcarz, M., Ossowski, P., Dziobek, K., and Strojny, D. (2025). miRNA-Mediated Regulation of Extracellular Matrix Dynamics across Breast Cancer Subtypes. Arch. Med. Sci.","DOI":"10.5114\/aoms\/205734"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16211","DOI":"10.1038\/s41598-025-00343-5","article-title":"Impact of MiRNAs on Wnt-Related Gene Activity in Breast Cancer","volume":"15","author":"Sirek","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Sirek, T., Sirek, A., Borawski, P., Zmarz\u0142y, N., Su\u0142kowska, J., Kr\u00f3l-Jatr\u0119ga, K., Op\u0142awski, M., Boro\u0144, D., Chalcarz, M., and Ossowski, P. (2024). miRNAs in Signal Transduction of SMAD Proteins in Breast Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810088"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An Online Database for Prediction of Functional microRNA Targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"eaav1741","DOI":"10.1126\/science.aav1741","article-title":"The Biochemical Basis of microRNA Targeting Efficacy","volume":"366","author":"McGeary","year":"2019","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A Flexible Statistical Power Analysis Program for the Social, Behavioral, and Biomedical Sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_95","first-page":"100625","article-title":"Integrated Analysis of Public Datasets for the Discovery and Validation of Survival-Associated Genes in Solid Tumors","volume":"5","year":"2024","journal-title":"Innovation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/bph.16257","article-title":"Transcriptome-Level Discovery of Survival-Associated Biomarkers and Therapy Targets in Non-Small-Cell Lung Cancer","volume":"181","year":"2024","journal-title":"Br. J. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:25:56Z","timestamp":1778520356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":96,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27094055"],"URL":"https:\/\/doi.org\/10.3390\/ijms27094055","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}