Abstract
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.