Metabolic dysfunction and metformin modify plasma extracellular vesicle signaling to prostate cancer cells

Metabolic dysfunction in type 2 diabetes is linked to altered plasma extracellular vesicle miRNA signaling to prostate cancer cells, with metformin reducing EV-driven tumor progression activity.

• Why it matters: T2D is associated with different outcomes in established prostate cancer, but the circulating signals and how metformin shifts them are unclear.
• What they did: Plasma EV-derived miRNAs were profiled in six T2D and six non-diabetic donors, and selected mimics were tested in DU145 cells for ZEB1 transcription; EV-enriched fractions were also assessed by RNA sequencing. DU145 cells were further exposed to EV-derived RNA from high fat diet (HFD) mice with or without metformin.
• The result: miR-192-5p and miR-106b-5p increased ZEB1, while miR-29b-3p did not; T2D EV exposure produced broad aggressive pathway responses. In HFD mice, metformin lowered DU145 migration (12.23% vs 20.25%; n=3/group; Welch P=0.0246) and Matrigel invasion (4.89% vs 7.89%; n=3/group; Welch P=0.0302).

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