{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:14:47Z","timestamp":1788275687601,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Deficiency of IL-36 Receptor Antagonist (DITRA) is a rare monogenic autoinflammatory disease, characterized by dysregulation of IL-36 signaling and phenotypically classified as a subtype of generalized pustular psoriasis. Objectives: This study aimed to explore the role of potentially coding and non-coding RNAs (ncRNAs) in the IL36RN interactome to identify putative pathogenic mechanisms, biomarkers, and therapeutic targets for DITRA. Methods: A systems biology approach was applied using the STRING database to construct the IL36RN protein\u2013protein interaction network. Key ncRNA interactions were identified using RNAInter. The networks were visualized and analyzed with Cytoscape v3 and the CytoHubba plugin to identify central nodes and interaction hubs. Pathway enrichment analysis was then performed to determine the biological relevance of candidate ncRNAs and genes. Results: Analysis identified thirty-eight ncRNAs interacting with the IL36RN network, including six lncRNAs and thirty-two miRNAs. Of these, thirty-three were associated with key DITRA-related signaling pathways, while five remain to be validated. Additionally, seven protein-coding genes were highlighted, with three (TINCR, PLEKHA1, and HNF4A) directly implicated in biological pathways related to DITRA. Many of the identified ncRNAs have prior associations with immune-mediated diseases, including psoriasis, supporting their potential relevance in DITRA pathogenesis. Conclusions: This study provides novel insights into the ncRNA-mediated regulation of IL36RN and its network in the context of DITRA. The findings support the potential utility of specific ncRNAs and genes, such as TINCR, PLEKHA1, and HNF4A, as key genomic elements warrant further functional characterization to confirm their mechanistic roles and may inform biomarker discovery and targeted therapeutic development in DITRA.<\/jats:p>","DOI":"10.3390\/genes16070753","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T09:29:01Z","timestamp":1751362141000},"page":"753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding Non-Coding RNA Regulators in DITRA: From Genomic Insights to Potential Biomarkers and Therapeutic Targets"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4160-3789","authenticated-orcid":false,"given":"Sofia","family":"Spanou","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-8071","authenticated-orcid":false,"given":"Athena","family":"Andreou","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"},{"name":"Department of Biomedical Sciences, School of Health Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2698-9772","authenticated-orcid":false,"given":"Katerina","family":"Gioti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Health Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2313-1305","authenticated-orcid":false,"given":"Dimitrios","family":"Chaniotis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Health Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-0528","authenticated-orcid":false,"given":"Apostolos","family":"Beloukas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Health Sciences, University of West Attica, 12243 Egaleo, Greece"},{"name":"National AIDS Reference Centre of Southern Greece, School of Public Health, University of West Attica, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9577-9923","authenticated-orcid":false,"given":"Louis","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Health Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6894-0774","authenticated-orcid":false,"given":"Trias","family":"Thireou","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.7861\/clinmed.2021-0257","article-title":"Psoriasis: A brief overview","volume":"21","author":"Raharja","year":"2021","journal-title":"Clin. 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