{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T20:24:36Z","timestamp":1785011076437,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81960305"],"award-info":[{"award-number":["81960305"]}]},{"name":"National Natural Science Foundation of China","award":["81460255"],"award-info":[{"award-number":["81460255"]}]},{"name":"National Natural Science Foundation of China","award":["61671098"],"award-info":[{"award-number":["61671098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein\u2013protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell\u2013cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1\u03b2. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1\u03b2 were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis.<\/jats:p>","DOI":"10.3390\/ijms232315286","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:13:12Z","timestamp":1670206392000},"page":"15286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of Novel Hub Genes Associated with Psoriasis Using Integrated Bioinformatics Analysis"],"prefix":"10.3390","volume":"23","author":[{"given":"Qi","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8255-433X","authenticated-orcid":false,"given":"Zhaoxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanxin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tokuyama, M., and Mabuchi, T. (2020). New Treatment Addressing the Pathogenesis of Psoriasis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207488"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kamiya, K., Kishimoto, M., Sugai, J., Komine, M., and Ohtsuki, M. (2019). Risk Factors for the Development of Psoriasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184347"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rendon, A., and Sch\u00e4kel, K. (2019). Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061475"},{"key":"ref_4","first-page":"97","article-title":"Current Developments in the Immunology of Psoriasis","volume":"93","author":"Kerstan","year":"2020","journal-title":"Yale J. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lu, X.-Q., Zhang, J.-Q., Zhang, S.-X., Qiao, J., Qiu, M.-T., Liu, X.-R., Chen, X.-X., Gao, C., and Zhang, H.-H. (2021). Identification of Novel Hub Genes Associated with Gastric Cancer Using Integrated Bioinformatics Analysis. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08358-7"},{"key":"ref_6","first-page":"93","article-title":"Prediction of Crucial Epigenetically-associated, Differentially Expressed Genes by Integrated Bioinformatics Analysis and the Identification of S100A9 as a Novel Biomarker in Psoriasis","volume":"45","author":"Wang","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40659-020-00275-6","article-title":"LncRNA SNHG7\/MiR-34a-5p\/SYVN1 Axis Plays a Vital Role in Proliferation, Apoptosis and Autophagy in Osteoarthritis","volume":"53","author":"Tian","year":"2020","journal-title":"Biol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"617","DOI":"10.2337\/db18-0313","article-title":"Identification of Specific MiRNAs in Neutrophils of Type 2 Diabetic Mice: Overexpression of MiRNA-129-2-3p Accelerates Diabetic Wound Healing","volume":"68","author":"Umehara","year":"2019","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1111\/cas.14910","article-title":"The Roles and Regulation of the KLF5 Transcription Factor in Cancers","volume":"112","author":"Luo","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/jdv.13854","article-title":"A Systematic Review of Worldwide Epidemiology of Psoriasis","volume":"31","author":"Michalek","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_11","first-page":"8623","article-title":"Beyond Self-Cleaning: Next Generation Smart Nanoscale Manipulators and Prospects for Subsea Production System","volume":"17","author":"Wang","year":"2017","journal-title":"Interface Focus"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.intimp.2021.107843","article-title":"Crosstalk between Wnt\/beta-catenin signaling and NF-kappaB signaling contributes to apical periodontitis","volume":"98","author":"Guan","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1111\/exd.14323","article-title":"Keratinocyte-Derived IL-1\u03b2 Induces PPARG Downregulation and PPARD Upregulation in Human Reconstructed Epidermis Following Barrier Impairment","volume":"30","author":"Blunder","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sobolev, V., Nesterova, A., Soboleva, A., Mezentsev, A., Dvoriankova, E., Piruzyan, A., Denisova, E., Melnichenko, O., and Korsunskaya, I. (2021). Analysis of PPAR\u03b3 Signaling Activity in Psoriasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168603"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3233\/CBM-171160","article-title":"Screening and Function Analysis of Hub Genes and Pathways in Hepatocellular Carcinoma via Bioinformatics Approaches","volume":"22","author":"Zhang","year":"2018","journal-title":"CBM"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113551","DOI":"10.1016\/j.jep.2020.113551","article-title":"Clinical Trait-Connected Network Analysis Reveals Transcriptional Markers of Active Psoriasis Treatment with Liangxue-Jiedu Decoction","volume":"268","author":"Li","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","first-page":"542","article-title":"CDKN3 Promotes Cell Proliferation, Invasion and Migration by Activating the AKT Signaling Pathway in Esophageal Squamous Cell Carcinoma","volume":"19","author":"Yu","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12943-021-01314-w","article-title":"Circular RNA CircSDHC Serves as a Sponge for MiR-127-3p to Promote the Proliferation and Metastasis of Renal Cell Carcinoma via the CDKN3\/E2F1 Axis","volume":"20","author":"Cen","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.biopha.2017.11.112","article-title":"Cyclin-Dependent Kinase Inhibitor 3 (CDKN3) Plays a Critical Role in Prostate Cancer via Regulating Cell Cycle and DNA Replication Signaling","volume":"96","author":"Yu","year":"2017","journal-title":"Biomed. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.tibs.2012.12.003","article-title":"Enigmatic Roles of Mcm10 in DNA Replication","volume":"38","author":"Thu","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e29118","DOI":"10.7554\/eLife.29118","article-title":"Mcm10 Promotes Rapid Isomerization of CMG-DNA for Replisome Bypass of Lagging Strand DNA Blocks","volume":"6","author":"Langston","year":"2017","journal-title":"eLife"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1111\/cas.14776","article-title":"MCM10 Compensates for Myc-Induced DNA Replication Stress in Breast Cancer Stem-like Cells","volume":"112","author":"Murayama","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Han, Z., Li, L., Huang, Y., Zhao, H., and Luo, Y. (2021). PBK\/TOPK: A Therapeutic Target Worthy of Attention. Cells, 10.","DOI":"10.3390\/cells10020371"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Huang, H., Lee, M.-H., Liu, K., Dong, Z., Ryoo, Z., and Kim, M.O. (2021). PBK\/TOPK: An Effective Drug Target with Diverse Therapeutic Potential. Cancers, 13.","DOI":"10.3390\/cancers13092232"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10657","DOI":"10.1096\/fj.202000770RR","article-title":"Autophagy Plays a Positive Role in Induction of Epidermal Proliferation","volume":"34","author":"Wang","year":"2020","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Qiu, X., Zheng, L., Liu, X., Hong, D., He, M., Tang, Z., Tian, C., Tan, G., Hwang, S., and Shi, Z. (2021). ULK1 Inhibition as a Targeted Therapeutic Strategy for Psoriasis by Regulating Keratinocytes and Their Crosstalk With Neutrophils. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.714274"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Swindell, W., Xing, X., Stuart, P., Chen, C., Aphale, A., Nair, R., Voorhees, J., Elder, J., Johnston, A., and Gudjonsson, J. (2012). Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034594"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1093\/abbs\/gmw036","article-title":"Dysregulated expression of inflammation-related genes in psoriatic dermis mesenchymal stem cells","volume":"48","author":"Niu","year":"2016","journal-title":"Acta Biochim. Biophys. Sin. (Shanghai)"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The Sva Package for Removing Batch Effects and Other Unwanted Variation in High-Throughput Experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/bioinformatics\/btg405","article-title":"Affy\u2014Analysis of Affymetrix GeneChip Data at the Probe Level","volume":"20","author":"Gautier","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4516349","DOI":"10.1155\/2020\/4516349","article-title":"Bioinformatic Analysis of Neuroimmune Mechanism of Neuropathic Pain","volume":"2020","author":"Yu","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New Perspectives on Genomes, Pathways, Diseases and Drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"i436","DOI":"10.1093\/bioinformatics\/btz363","article-title":"Comprehensive Evaluation of Transcriptome-Based Cell-Type Quantification Methods for Immuno-Oncology","volume":"35","author":"Sturm","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust Enumeration of Cell Subsets from Tissue Expression Profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1533033820928471","DOI":"10.1177\/1533033820928471","article-title":"Circular RNA Hsa_circ_0000376 Participates in Tumorigenesis of Breast Cancer by Targeting MiR-1285-3p","volume":"19","author":"Peng","year":"2020","journal-title":"Technol. Cancer Res. Treat."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15286\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:33:42Z","timestamp":1760146422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,4]]},"references-count":35,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232315286"],"URL":"https:\/\/doi.org\/10.3390\/ijms232315286","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,4]]}}}