{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:16:49Z","timestamp":1790083009708,"version":"4.0.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Mitochondrial dysfunction has been implicated in the pathogenesis of dermatomyositis (DM), a rare autoimmune disease affecting the skin and muscles. However, the genetic basis underlying dysfunctional mitochondria and the development of DM remains incomplete.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The datasets of DM muscle and skin tissues were retrieved from the Gene Expression Omnibus database. The mitochondrial related genes (MRGs) were retrieved from MitoCarta. DM-related modules in muscle and skin tissues were identified with the analysis of weighted gene co-expression network (WGCNA), and then compared with the MRGs to obtain the overlapping mitochondrial related module genes (mito-MGs). Subsequently, differential expression genes (DEGs) obtained from muscle and skin datasets were overlapped with MRGs to identify mitochondrial related DEGs (mito-DEGs). Next, functional enrichment analysis was applied to analyze possible relevant biological pathways. We used the Jvenn online tool to intersect mito-MGs with mito-DEGs to identify hub genes and validate them using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry staining. In addition, we evaluated immune infiltration in muscle and skin tissues of DM patients using the one-sample gene set enrichment analysis (ssGSEA) algorithm and predicted potential transcription factor (TF) -gene network by NetworkAnalyst.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The WGCNA analysis revealed 105 mito-MGs, while the DEG analysis identified 3 mito-DEGs. These genes showed functional enrichment for amino acid metabolism, energy metabolism and oxidative phosphorylation. Through the intersection analysis of the mito-MGs from the WGCNA analysis and the mito-DEGs from the DEG set, three DM mito-hub genes (<jats:italic>IFI27<\/jats:italic>, <jats:italic>CMPK2<\/jats:italic>, and <jats:italic>LAP3<\/jats:italic>) were identified and validated by RT-qPCR and immunohistochemistry analysis. Additionally, positive correlations were observed between hub genes and immune cell abundance. The TF-hub gene regulatory network revealed significant interactions involving ERG, VDR, and ZFX with <jats:italic>CMPK2<\/jats:italic> and <jats:italic>LAP3<\/jats:italic>, as well as SOX2 with <jats:italic>LAP3<\/jats:italic> and <jats:italic>IFI27<\/jats:italic>, and AR with <jats:italic>IFI27<\/jats:italic> and <jats:italic>CMPK2<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The mito-hub genes (<jats:italic>IFI27<\/jats:italic>, <jats:italic>CMPK2<\/jats:italic>, and <jats:italic>LAP3<\/jats:italic>) are identified in both muscles and skin tissues from DM patients. These genes may be associated with immune infiltration in DM, providing a new entry point for the pathogenesis of DM.<\/jats:p>","DOI":"10.3389\/fgene.2024.1325035","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T05:21:10Z","timestamp":1707369670000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Mitochondrial-related hub genes in dermatomyositis: muscle and skin datasets-based identification and in vivo validation"],"prefix":"10.3389","volume":"15","author":[{"given":"Shuo","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s10735-004-2194-6","article-title":"Mitochondrial abnormalities in dermatomyositis: characteristic pattern of neuropathology","volume":"35","author":"Alhatou","year":"2004","journal-title":"J. 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