MicroRNAs (miRs) have a critical role in the development and malignant progression of osteosarcoma (OS), but the underlying mechanisms have largely remained elusive. The present study aimed to explore the regulatory role of miR‑138 in OS growth and metastasis and investigated the associated mechanisms. Reverse‑transcription quantitative polymerase chain reaction and western blot analysis were performed to examine the miR‑138 and protein expression levels in OS and normal bone tissues and cell lines. An MTT assay and a Transwell assay were used to assess cell proliferation and invasion. Flow cytometry was used to analyze the cell cycle and determine the apoptotic rate. A luciferase reporter assay was used to confirm the targeting association between miR‑138 and tumor necrosis factor‑α‑induced protein 8 (TNFAIP8). It was found that miR‑138 was downregulated in OS tissues and cell lines. Overexpression of miR‑138 decreased the proliferation, cell cycle progression and invasion of OS cells, while inducing cell apoptosis. TNFAIP8 was then identified as a novel target of miR‑138. Similarly to the effects of miR‑138 overexpression, inhibition of TNFAIP8 also inhibited OS cell proliferation, cell cycle progression and invasion, and induced cell apoptosis. In addition, miR‑138 overexpression as well as downregulation of TNFAIP8 reduced OS cell invasion via inhibition of matrix metalloproteinase‑2 and ‑9 expression. Taken together, the results of the present study demonstrated that miR‑138 directly targets TNFAIP8 and acts as a tumor suppressor in OS, suggesting that the miR‑138/TNFAIP8 interaction may become a promising therapeutic target for OS.

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