{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:02:04Z","timestamp":1782205324934,"version":"3.54.5"},"reference-count":77,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Perugia, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Osteosarcoma (OS) and extraskeletal osteosarcoma (EOS) in dogs exhibit histological similarities but differ in anatomical origin, which poses a challenge to diagnostic accuracy. We adopted a marker-first strategy to enhance molecular classification by selecting RUNX2, KPNA2, and SATB2, three validated immunohistochemical (IHC) markers, as primary targets. Bioinformatic screening identified the miR-30 family as the only miRNA group predicted to coordinately regulate RUNX2, KPNA2, and SATB2, justifying its prioritization for expression analysis. RT-qPCR on FFPE tissues from 14 OS, 19 EOS, and 10 healthy controls revealed that miR-30a was significantly downregulated in OS and inversely correlated with RUNX2 nuclear expression, confirmed by IHC. MiR-30e also showed high diagnostic accuracy, while miR-30b and miR-30c distinguished EOS from OS. Non-seed interaction modeling (i.e., outside the canonical \u201cseed\u201d region, spanning nucleotides 2\u20138 of the miRNA) suggested divergent regulatory affinities within the PI3K\/AKT\/RUNX2 axis among miR-30 family members. MiR-30a and miR-30e exhibited the highest diagnostic power (LR+ 7.7 and 6.8, respectively), supporting their role as biomarkers. These results highlight a miR\u201330\u2013centered regulatory axis with relevance for diagnosis and molecular stratification of canine osteogenic tumors.<\/jats:p>","DOI":"10.3390\/cells14161279","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T13:28:22Z","timestamp":1755523702000},"page":"1279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A miR-30 Guided Molecular Profiling of Canine Osteosarcoma and Extraskeletal Osteosarcoma Reveals Non-Seed Regulatory Divergence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3695-9275","authenticated-orcid":false,"given":"Gabriella","family":"Guelfi","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, Universit\u00e0 degli Studi di Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petronela","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Universit\u00e0 degli Studi di Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-6245","authenticated-orcid":false,"given":"Camilla","family":"Capaccia","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Universit\u00e0 degli Studi di Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-6739","authenticated-orcid":false,"given":"Ilaria","family":"Porcellato","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Universit\u00e0 degli Studi di Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3680-0926","authenticated-orcid":false,"given":"Elisabetta","family":"Manuali","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Veterinary Histopathology, Istituto Zooprofilattico dell\u2019Umbria e delle Marche (IZSUM) Togo Rosati, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1727-4118","authenticated-orcid":false,"given":"Margherita","family":"Maranesi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Universit\u00e0 degli Studi di Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-9275","authenticated-orcid":false,"given":"Leonardo","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Universit\u00e0 degli Studi di Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.pathol.2022.10.002","article-title":"Primary Cutaneous Extraskeletal Osteosarcoma: A Series of 16 Cases","volume":"55","author":"Habeeb","year":"2023","journal-title":"Pathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"300639","DOI":"10.1016\/j.hpr.2022.300639","article-title":"Extraskeletal Osteosarcoma and Its Histological Mimics","volume":"28","author":"Yenwongfai","year":"2022","journal-title":"Hum. 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