Abstract
Osteoclastogenesis is the rate-limiting step in tumor osteolytic metastasis. MicroRNAs play crucial roles in tumor progression and osteoclastogenesis regulation. Recent studies have demonstrated that exosomes are able to function as messengers that deliver microRNAs between cells. However, the effects of lung adenocarcinoma cell-derived exosomal miRNAs in osteoclastogenesis remain poorly understood. In this study, we found that exosomes derived from A549 cells facilitate osteoclastogenesis. As miR-21 was involved in tumorigenesis and osteoclastogenesis, we further proved the existence of miR-21 in A549 cell-derived exosomes and investigated its function. MiR-21 overexpression in A549 cells led to increased levels of miR-21 in exosomes and facilitated osteoclastogenesis. Conversely, miR-21 depletion in A549 cells down-regulated miR-21 in exosomes and alleviated osteoclastogenesis. Mechanical experiments demonstrated that exosomal miR-21 exerted its promoting effects on osteoclastogenesis via targeting Pdcd4, which is a known target of miR-21 and a regulator of osteoclastogenesis. Finally, clinical data showed that higher miR-21 levels were associated with a worse overall survival in lung adenocarcinoma patients. In conclusion, we found that lung adenocarcinoma derived exosomal miR-21 may facilitate osteoclastogenesis, which suggests that it is a potential therapeutic target of bone metastasis.