Recent studies have demonstrated that microRNA-183 (miR-183) deregulates and plays major roles in many tumors. However, the role of miR-183 in osteosarcoma (OS) pathogenesis is still largely unknown. In this study, we first over-expressed and knocked down miR-183 in MG63 and U2OS cells, respectively. Functional analyses showed that ectopic expression of miR-183 suppressed MG63 cell growth, migration, and invasion in vitro and in vivo, whereas knockdown of endogenous miR-183 in U2OS cells significantly enhanced these abilities. Next, we characterized low density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-183 that interacted with the 3'-untranslated region of LRP6. Furthermore, ectopic expression of LRP6 significantly abrogated the tumor-suppressive effect induced by miR-183. Finally, miR-183 regulated the tumor-suppressive functions in MG63 cells by suppressing the LRP6-Wnt/beta-catenin signaling pathway. Therefore, our study demonstrates that miR-183 is a tumor suppressor microRNA that plays a major role in OS. (C) 2018 Elsevier Inc. All rights reserved.