PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>κ</mml:mi></mml:mrow></mml:math>B Signaling Pathway

Abstract

Prostate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient’s quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cell interaction. However, the impact of cancer-derived exosomes on bone cells remains unclear. Herein, we isolated exosomes from prostate cancer cell line PC-3 and investigated their effects on human osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. The potential mechanism was evaluated by qRT-PCR, western blotting, and microRNA transfection experiments. The results showed that PC-3-derived exosomes dramatically inhibited osteoclast differentiation. Marker genes of mature osteoclasts, including CTSK, NFATc1, ACP5, and miR-214, were all downregulated in the presence of PC-3 exosomes. Furthermore, transfection experiments showed that miR-214 downregulation severely impaired osteoclast differentiation, whereas overexpression of miR-214 promoted differentiation. Furthermore, we demonstrated that PC-3-derived exosomes block the NF- κ B signaling pathway. Our study suggested that PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking the NF- κ B signaling pathway. Therefore, elevating miR-214 levels in the bone metastatic site may attenuate the invasion of prostate cancer.