{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T01:53:42Z","timestamp":1782870822268,"version":"3.54.5"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"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>Metastatic melanoma causes a high rate of mortality. We conducted an integrated analysis to identify critical regulators associated with the prognosis, pathogenesis, and targeted therapies of metastatic-melanoma. A microarray dataset, GSE15605, including 12 metastatic-melanoma and sixteen normal skin (NS) samples, were obtained from the GEO database. After exploration of DEGs of NS and metastatic-melanoma, identification of relevant transcription factors (TFs) and kinases, the Gene Ontology (GO), and pathways analyses of DEGs were performed. Protein-protein interaction (PPI) networks were evaluated by the STRING and Cytoscape. Subsequently, the hub genes were selected using GEPIA. Survival analysis was performed using the TCGA. To identify microRNA and lncRNA DEGs of the melanoma-associated genes miRwalk and FANTOM6 were employed. In metastatic-melanoma samples 285 and 1173 genes were up and down-regulated, respectively. The upregulated genes were mostly involved in granulocyte chemotaxis, positive regulation of calcium ion transmembrane transport, and melanin biosynthetic process. Five hub genes including CXCL11, ICAM1, LEF1, MITF, and STAT1 were identified, SUZ12, SOX2, TCF3, NANOG, and SMAD4 were determined as the most significant TFs in metastatic-melanoma. Furthermore, CDK2, GSK3B, CSNK2A1, and CDK1 target the highest amounts of genes associated with disease. The DGIdb analysis results show the match drugs for five hub genes. MiRNAs analysis revealed hsa-miR-181c-5p, hsa-miR-30b-3p, hsa-miR-3680-3P, hsa-miR-4659a-3p, hsa-miR-4687-3P, and hsa-miR-6808-3P could regulate the hub genes, whereas RP11-553K8.5 and SRP14-AS1 were identified as the top significant lncRNA. The items recognized in the current study can be used as potential biomarkers for diagnostic, predictive, and might helpful to develop targeted combined therapies.<\/jats:p>","DOI":"10.1371\/journal.pone.0312754","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:34:48Z","timestamp":1737052488000},"page":"e0312754","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metastatic melanoma: An integrated analysis to identify critical regulators associated with prognosis, pathogenesis and targeted therapies"],"prefix":"10.1371","volume":"20","author":[{"given":"Zeinab","family":"Chaharlashkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousof","family":"Saeedi 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endogenous RNA for microRNA-625-5p and subsequently increasing IGF-1R expression","volume":"29","author":"L Wu","year":"2022","journal-title":"Cancer Gene Ther"},{"issue":"1","key":"pone.0312754.ref009","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1586\/1744666X.2016.1100965","article-title":"miRNAs in melanoma: a defined role in tumor progression and metastasis","volume":"12","author":"F Mannavola","year":"2016","journal-title":"Expert Rev Clin Immunol"},{"issue":"31","key":"pone.0312754.ref010","doi-asserted-by":"crossref","first-page":"49481","DOI":"10.18632\/oncotarget.10373","article-title":"Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer","volume":"7","author":"W Yang","year":"2016","journal-title":"Oncotarget"},{"issue":"3","key":"pone.0312754.ref011","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1002\/jcp.29067","article-title":"Identification of hub genes and construction of 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Analysis.","volume":"14","author":"X Xuan","year":"2021","journal-title":"Int J Gen Med."},{"issue":"1","key":"pone.0312754.ref015","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12957-019-1605-9","article-title":"Bioinformatic identification of candidate biomarkers and related transcription factors in nasopharyngeal carcinoma.","volume":"17","author":"Z Ye","year":"2019","journal-title":"World J Surg Oncol"},{"issue":"3","key":"pone.0312754.ref016","doi-asserted-by":"crossref","DOI":"10.1515\/jib-2019-0005","article-title":"Integrating Molecular Biology and Bioinformatics Education.","volume":"16","author":"B Pucker","year":"2019","journal-title":"J Integr Bioinform"},{"issue":"2","key":"pone.0312754.ref017","first-page":"903","article-title":"Identification of key candidate genes involved in melanoma metastasis","volume":"20","author":"J Chen","year":"2019","journal-title":"Mol Med 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Chen","year":"2012","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0312754.ref025","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12957-018-1409-3","article-title":"Identification of hub genes with prognostic values in gastric cancer by bioinformatics analysis","volume":"16","author":"T Li","year":"2018","journal-title":"World Journal of Surgical Oncology"},{"key":"pone.0312754.ref026","doi-asserted-by":"crossref","first-page":"153763","DOI":"10.1016\/j.prp.2022.153763","article-title":"MiR-181c suppresses triple-negative breast cancer tumorigenesis by targeting MAP4K4.","volume":"230","author":"D Xie","year":"2022","journal-title":"Pathology\u2014Research and Practice."},{"key":"pone.0312754.ref027","doi-asserted-by":"crossref","first-page":"155017","DOI":"10.1016\/j.prp.2023.155017","article-title":"Ectopic expression of tumor suppressive miR-181c-5p downregulates oncogenic Notch signaling in MDA-MB-231 cells.","volume":"253","author":"M Shuaib","year":"2024","journal-title":"Pathology\u2014Research and Practice"},{"issue":"2","key":"pone.0312754.ref028","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12920-019-0487-6","article-title":"The role of long non-coding RNAs in the pathogenesis of hereditary diseases","volume":"12","author":"P Sparber","year":"2019","journal-title":"BMC Med Genomics"},{"key":"pone.0312754.ref029","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.toxlet.2019.12.021","article-title":"Critical role of toll-like receptor 4 (TLR4) in ricin toxin-induced inflammatory responses in macrophages.","volume":"321","author":"M Dong","year":"2020","journal-title":"Toxicol Lett"},{"issue":"6","key":"pone.0312754.ref030","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1002\/jcp.30166","article-title":"The role of toll-like receptor 4 (TLR4) in cancer progression: A possible therapeutic target?","volume":"236","author":"B Kashani","year":"2021","journal-title":"J Cell 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O\u2019Shea","year":"2019","edition":"5"},{"issue":"1","key":"pone.0312754.ref034","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/pro.3987","article-title":"The Human Protein Atlas-Spatial localization of the human proteome in health and disease","volume":"30","author":"A Digre","year":"2021","journal-title":"Protein Sci"},{"key":"pone.0312754.ref035","doi-asserted-by":"crossref","first-page":"646252","DOI":"10.3389\/fcell.2021.646252","article-title":"CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer.","volume":"9","author":"Y Cao","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"24","key":"pone.0312754.ref036","doi-asserted-by":"crossref","first-page":"7569","DOI":"10.1158\/1078-0432.CCR-17-2008","article-title":"CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid TumorsCAR T Therapy in Advanced Thyroid Cancer","volume":"23","author":"IM Min","year":"2017","journal-title":"Clin Cancer 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Gajos-Michniewicz","year":"2016","journal-title":"Fitoterapia"},{"issue":"2","key":"pone.0312754.ref043","doi-asserted-by":"crossref","first-page":"e1085","DOI":"10.1038\/cddis.2014.13","article-title":"The LEF1\/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis in selenite-treated colorectal cancer cells","volume":"5","author":"P Wu","year":"2014","journal-title":"Cell Death Dis"},{"issue":"2","key":"pone.0312754.ref044","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.canlet.2011.08.012","article-title":"5-aza-2\u2019-deoxycytidine enhances susceptibility of renal cell carcinoma to paclitaxel by decreasing LEF1\/phospho-\u03b2-catenin expression","volume":"311","author":"D Shang","year":"2011","journal-title":"Cancer Lett"},{"issue":"16","key":"pone.0312754.ref045","doi-asserted-by":"crossref","first-page":"21631","DOI":"10.18632\/oncotarget.7795","article-title":"High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia 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Liu","year":"2020","journal-title":"Cell Death Dis"},{"issue":"2","key":"pone.0312754.ref049","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.3390\/ijms16024343","article-title":"Metastatic melanoma cells evade immune detection by silencing STAT1.","volume":"16","author":"JL Osborn","year":"2015","journal-title":"Int J Mol Sci"},{"issue":"7","key":"pone.0312754.ref050","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1007\/s13277-015-3195-7","article-title":"SUZ12 promotes gastric cancer cell proliferation and metastasis by regulating KLF2 and E-cadherin.","volume":"36","author":"R Xia","year":"2015","journal-title":"Tumour Biol."},{"issue":"1","key":"pone.0312754.ref051","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1038\/s41467-022-30264-0","article-title":"Inhibition of the CDK2 and Cyclin A complex leads to autophagic degradation of CDK2 in cancer cells","volume":"13","author":"J Zhang","year":"2022","journal-title":"Nature Communications"},{"issue":"3","key":"pone.0312754.ref052","doi-asserted-by":"crossref","first-page":"e7858","DOI":"10.15252\/msb.20177858","article-title":"Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors","volume":"14","author":"A Azimi","year":"2018","journal-title":"Mol Syst Biol"},{"issue":"1","key":"pone.0312754.ref053","first-page":"9","article-title":"Induction of G0\/G1 phase arrest and apoptosis by CRISPR\/Cas9-mediated knockout of CDK2 in A375 melanocytes.","volume":"12","author":"H Liu","year":"2020","journal-title":"Mol Clin Oncol."},{"issue":"1","key":"pone.0312754.ref054","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1158\/0008-5472.CAN-06-1538","article-title":"An organometallic protein kinase inhibitor pharmacologically activates p53 and induces apoptosis in human melanoma cells","volume":"67","author":"KS Smalley","year":"2007","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0312754.ref055","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/pros.23106","article-title":"GSK-3\u03b2 controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells","volume":"76","author":"A Sun","year":"2016","journal-title":"Prostate"},{"issue":"20","key":"pone.0312754.ref056","doi-asserted-by":"crossref","first-page":"5664","DOI":"10.1158\/0008-5472.CAN-17-0799","article-title":"GSK3 Inhibition Drives Maturation of NK Cells and Enhances Their Antitumor Activity","volume":"77","author":"F Cichocki","year":"2017","journal-title":"Cancer Res"},{"issue":"3","key":"pone.0312754.ref057","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.pan.2019.12.019","article-title":"Upregulated \u03b2-catenin signaling does not affect survival of pancreatic cancer cells during dual inhibition of GSK3B and HDAC.","volume":"20","author":"K Nesteruk","year":"2020","journal-title":"Pancreatology"},{"issue":"6","key":"pone.0312754.ref058","doi-asserted-by":"crossref","DOI":"10.3390\/cells9061388","article-title":"Glycogen Synthase Kinase 3\u03b2 in Cancer Biology and Treatment.","volume":"9","author":"T Domoto","year":"2020","journal-title":"Cells"},{"issue":"47","key":"pone.0312754.ref059","doi-asserted-by":"crossref","first-page":"77038","DOI":"10.18632\/oncotarget.12781","article-title":"Efficacy of glycogen synthase kinase-3\u03b2 targeting against osteosarcoma via activation of \u03b2-catenin.","volume":"7","author":"S Shimozaki","year":"2016","journal-title":"Oncotarget"},{"issue":"19","key":"pone.0312754.ref060","doi-asserted-by":"crossref","first-page":"8156","DOI":"10.1158\/0008-5472.CAN-08-1061","article-title":"Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha\/beta in pancreatic cancer","volume":"68","author":"W Wilson","year":"2008","journal-title":"Cancer Res"},{"issue":"22","key":"pone.0312754.ref061","doi-asserted-by":"crossref","first-page":"6810","DOI":"10.1158\/1078-0432.CCR-09-0973","article-title":"Deregulated GSK3{beta} sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase","volume":"15","author":"W Mai","year":"2009","journal-title":"Clin Cancer Res"},{"issue":"16","key":"pone.0312754.ref062","doi-asserted-by":"crossref","first-page":"6643","DOI":"10.1158\/0008-5472.CAN-08-0850","article-title":"Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation","volume":"68","author":"S Kotliarova","year":"2008","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0312754.ref063","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1158\/1535-7163.MCT-13-0681","article-title":"Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer","volume":"13","author":"K Pal","year":"2014","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"pone.0312754.ref064","doi-asserted-by":"crossref","first-page":"19977","DOI":"10.1038\/s41598-019-56461-4","article-title":"9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer","volume":"9","author":"H Kuroki","year":"2019","journal-title":"Scientific Reports"},{"issue":"2","key":"pone.0312754.ref065","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41419-021-03475-4","article-title":"Glycogen synthase kinase 3\u03b2 inhibition synergizes with PARP inhibitors through the induction of homologous recombination deficiency in colorectal cancer","volume":"12","author":"N Zhang","year":"2021","journal-title":"Cell Death Dis"},{"issue":"1","key":"pone.0312754.ref066","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41698-022-00260-0","article-title":"GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance 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