Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts

Qian Zhao,1,2,* Chang Liu,1,* Ying Xie,1 Mengjia Tang,1 Guojing Luo,1 Xiang Chen,1 Li Tian,1 Xijie Yu1 1Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of General Practice, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xijie YuLaboratory of Endocrinology and Metabolism, Department of Endocrinology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu 610041, People’s Republic of ChinaTel +86-28-8542-2362Fax +86-28-8542-3459Email xijieyu@hotmail.comObjective: Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that some miRNAs could regulate cancers progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical significance in BM patients.Materials and Methods: The difference of miRNA expression in two lung cancer cell lines SBC-5 (with characteristic BM ability) and SBC-3 (without BM ability) were analyzed by microarray and qRT-PCR. Circulating miR-21 levels of lung cancer patients with or without BM were compared by qRT-PCR. The TRAP staining was used to investigate the effects of conditioned media from lung cancer cell lines or patients’ plasma with different miR-21 levels on osteoclastogenesis. ROC curve was used to evaluate the diagnostic performance of circulating miR-21 in BM patients.Results: We found that miR-21 expression was specifically higher in SBC-5 than that in SBC-3 cells. The supernatants of SBC-5 cells with higher-level miR-21 promoted osteoclastogenesis. Moreover, we demonstrated that the circulating miR-21 level was significantly higher in BM patients than that in non-BM patients. The plasma from BM patients with higher-level miR-21 could also promote osteoclastogenesis. Mechanistically, lung cancer cells-derived circulating miR-21 could be transferred into osteoclast precursor cells and promote osteoclastogenesis probably by inhibiting PTEN. Finally, clinical data showed that circulating miR-21 had a potential for the diagnosis of BM.Conclusion: Overall, our findings suggested that circulating miR-21 played important roles in osteoclastogenesis of lung cancer patients and may serve as a biomarker to diagnose BM of lung cancer.Keywords: microRNA, bone metastasis, lung cancer, osteoclast, biomarker