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Molecular subtypes of bone metastatic PC (MetA-C) were recently identified, with the proliferation-driven MetB subtype linked to very poor prognosis. Non-coding microRNAs (miRs) regulate gene expression and constitute potential therapeutic targets. This study aimed to explore miR profiles in bone metastases in relation to the MetA-C subtypes, with focus on the aggressive MetB subtype. Genome-wide microarray analysis of clinical bone metastasis samples (n\u2009=\u200996, 62 patients) identified miR-375 to be inversely associated with the MetB subtype. The metastatic C4-2B cell line was transduced to overexpress or sequester miR-375 and effects were evaluated by microarray analysis, cell proliferation\/adhesion assays, and tumor growth in mice. miR-375 overexpression in C4-2B altered transcription profiles and shifted the phenotype from being MetB-like to becoming MetA-like. In cell culture, miR-375 overexpression reduced cell proliferation, increased adhesion, and downregulated\n                    <jats:italic>YAP1<\/jats:italic>\n                    expression among other direct gene targets, while miR-375 inhibition had opposite effects. In mice, miR-375 overexpression reduced tumor establishment and growth. Our data link clinical and experimental findings of miR-375 being a potential inhibitor of the aggressive MetB subtype in PC.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-67032-9","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:53:36Z","timestamp":1787680416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA profiles of prostate cancer bone metastases and miR-375 as an inhibitor of the aggressive metastasis subtype MetB"],"prefix":"10.1038","volume":"16","author":[{"given":"Helena","family":"J\u00e4remo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Semenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Halin Bergstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Thysell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lundholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Freyhult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Josefsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Wel\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Thellenberg Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sead","family":"Crnalic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Bergh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Brattsand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-1999","authenticated-orcid":false,"given":"Pernilla","family":"Wikstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"67032_CR1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.eururo.2024.11.013","volume":"87","author":"EJ Schafer","year":"2025","unstructured":"Schafer, E. 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