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Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>SOX10 is essential for melanocyte development and maintenance and plays a critical role in uveal melanoma (UM) initiation and progression. While SOX10\u2019s transcriptional regulation of protein-coding genes is well characterized, its role on microRNA (miRNA) regulatory landscape in UM remains unexplored. Here, we employed network-based modeling to systematically characterize miRNA regulatory functions following SOX10 depletion in UM. First, we profiled mRNA and miRNA expression levels in SOX10 wild-type and knockdown UM cells. Then, we integrated the transcriptomic data, a UM network, and a Bayesian model to quantify miRNAs\u2019 regulatory activities and identify key miRNAs. Subsequently, we employed pathway enrichment analysis combined with literature mining to elucidate the functional roles of identified miRNAs through their target genes and associated signaling pathways in UM. We identified 17 miRNAs that show significant changes in regulatory activities following SOX10 knockdown in UM cells. These miRNAs regulate the expression of genes involved in cancer hallmark pathways, including cell cycle progression, mTORC1 signaling, and fatty acid metabolism. Notably, miR-34a, miR-25, miR-186, and miR-211 have tumor-suppressive potential by targeting genes involved in UM progression and metastasis. Our computational analysis suggests that SOX10 depletion in UM reshapes the miRNA regulatory landscape in a manner potentially consistent with tumor-suppressive activity, requiring experimental validation.<\/jats:p>","DOI":"10.1007\/s00018-026-06239-5","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:47:22Z","timestamp":1778633242000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network-based analysis reveals potential microRNA regulation of oncogenic pathways in SOX10-depleted uveal melanoma"],"prefix":"10.1007","volume":"83","author":[{"given":"Chunyan","family":"Luan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Wessely","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhesi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Weich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Lischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carola","family":"Berking","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus V.","family":"Heppt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio","family":"Vera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4913-5822","authenticated-orcid":false,"given":"Xin","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"issue":"1","key":"6239_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41572-020-0158-0","volume":"6","author":"MJ Jager","year":"2020","unstructured":"Jager MJ, Shields CL, Cebulla CM, Abdel-Rahman MH, Grossniklaus HE, Stern M-H, Carvajal RD, Belfort RN, Jia R, Shields JA et al (2020) Uveal melanoma. 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CB is a board member of the Dermatologic Cooperative Oncology group (DeCOG). MH received honoraria for lectures and presentations from Novartis, BMS, MSD, and Immunocore and participated on data safety monitoring boards or advisory boards of Novartis, BMS, MSD, and Immunocore. The other authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"206"}}