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miR‐134 has been shown to be associated with angiogenesis and the progression of osteosarcoma. This study further assessed the effects of miR‐134 expression on osteosarcoma cell migration, invasion, and metastasis in vitro and in a nude mouse xenograft model, exploring the underlying molecular events. Luciferase reporter assays revealed that miR‐134 directly targets the 3′‐UTRs of MMP1 and MMP3 to reduce their expression in osteosarcoma cells. In conclusion, overexpression of miR‐134 suppresses osteosarcoma cell invasion and metastasis through the inhibition of MMP1 and MMP3 expression. We propose miR‐134 as an attractive novel therapeutic target for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]