Exosomes Derived from PC-3 Cells Suppress Osteoclast Differentiation by Downregulating MiR-148a and Blocking the PI3K/AKT/mTOR Pathway

Prostate cancer is a leading malignancy in men that can also disrupt the bone tissue balance. Among all urological cancers, prostate cancer is associated with the highest rate of bone metastases, which can greatly reduce a patient's quality of life. In recent years, cell-derived exosomes, which can contain a wide range of biologically active molecules, have been reported as a novel method of communication among individual cells. However, the specific role that exosomes serve in this disease has not been fully elucidated. The prostate cancer cell line PC-3 were applied in the present study, where its exosomes were isolated to explore their potential effects on osteoclast differentiation. Exosomes are extracellular vesicles secreted by cells. The size of exosomes is 30-150 nm. They have double membrane structure and saucer-like morphology. They contain rich contents (including nucleic acid, protein and lipid) and participate in molecular transmission between cells. The combined results of tartrate-resistant acid phosphatase staining (to identify osteoclasts obtained from human peripheral blood mononuclear cells), reverse transcription-quantitative PCR and western blotting showed that PC-3-derived exosomes attenuated osteoclast differentiation by downregulating marker genes associated with osteoclastic maturation, including V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, matrix metalloproteinase 9 and integrin β3. microRNA (miR)-148a expression was also found to be downregulated in osteoclasts by PC-3-derived exosomes. In addition, the mTOR and AKT signaling pathways were blocked after exposure to these PC-3 cell-derived exosomes. Therefore, results from the present study suggest that miR-148a mimics may be a new therapeutic approach for the prevention of prostate cancer bone metastases.