Tumor suppressor miR-124 involved in stromal cells growth and apoptosis by targeting RANKL in giant cell tumor of bone

Giant cell tumor of bone (GCTB) is an aggressive skeletal neoplasm and exhibits malignant bone lytic behavior. However, little is known regarding the molecular mechanisms of GCTB at present. Accumulating evidences demonstrate that microRNAs (miRNAs) play essential roles in various tumors through regulating their target genes. MicroRNA-124 (miR-124) is reported as a tumor suppressor in many human cancers, but little is known about its function in GCTB. In this study, we showed that miR-124 was more frequently down-regulated in GCTB tissues. Down-expression of miR-124 was positively associated with tumor extension (P = 0.000) and grade (P = 0.000). Further in vitro researches proved that restoration of miR-124 suppressed giant-cell tumor stromal cells (GCTSCs) growth and induced apoptosis, whereas exogenous knock-down of miR-124 promoted GCTSCs proliferation and inhibited apoptosis. Moreover, mechanistic studies identified that miR-124 could regulate the expression of RANKL by directly binding to its 3'-UTR region. Thus, our results indicated that miR-124 could directly target RANKL and participate in growth and apoptosis in the GCTSCs, which suggested that miR-124 may be a new and potential therapeutic target for the GCTB treatment.