Exosomal miR-1275 Secreted by Prostate Cancer Cells Modulates Osteoblast Proliferation and Activity by Targeting the SIRT2/RUNX2 Cascade

Prostate cancer (PCa) is one of the most frequently diagnosed malignancies and the second leading cause of cancer mortality among men worldwide. Modulation of osteoblast activity is involved in PCa metastasis, and miR-1275 is also reported to regulate PCa metastasis; however, the association between cancer-derived exosomal miR-1275 and osteoblast activity is unclear. Here, we isolated exosomes from PC3-derived conditioned medium by ultracentrifugation. We found that miR-1275 could be transferred from PCa cells to osteoblasts via exosomes. Exosomal miR-1275 significantly accelerated the proliferation of osteoblasts and the expression levels of osteoblast-specific genes, such as osteocalcin (OCN), type I collagen (COL-1), and osteopontin (OPN). Moreover, exosomal miR-1275 increased the expression of RUNX2, a master modulator of osteoblast activity, by down-regulation of SIRT2, which in turn influenced the growth and activity of osteoblasts. Our findings indicate that PCa-derived exosomal miR-1275 promotes the proliferation and activity of osteoblasts via modulation of SIRT2/Runx2 signaling.