MicroRNA profiles of prostate cancer bone metastases and miR-375 as an inhibitor of the aggressive metastasis subtype MetB.

Järemo H, Semenas J, Halin Bergström S, Thysell E, Lundholm M, Freyhult E, Josefsson A, Welén K, Thellenberg Karlsson C, Crnalic S, Bergh A, Brattsand M, Wikström P

Sci Rep 16 (1) - [2026-08-25; online 2026-08-25]

Novel treatments for metastatic prostate cancer (PC) are needed. 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 = 96, 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 YAP1 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.

Bioinformatics (NBIS) [Collaborative]

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PubMed 42642447

DOI 10.1038/s41598-026-67032-9

Crossref 10.1038/s41598-026-67032-9

pmc: PMC13507049
pii: 10.1038/s41598-026-67032-9