Gliomas are the most common primary malignant brain tumor in adults. Although these tumors are aggressive and frequently lethal, there are currently few therapeutic approaches available to prolong patient survival. MicroRNAs play important roles in regulating the expression of genes that control diverse cellular processes. Here, we investigated the expression and function of miR-139-3p in gliomas using clinical specimens, cultured cells, and a mouse xenograft tumor model. We found that miR-139-3p expression is markedly lower in human glioma tissues than in normal brain tissues. We identified melanoma differentiation-associated gene-9 (MDA-9)/syntenin, an adaptor protein implicated in tumor metastasis, as a novel direct target of miR-139-3p and showed that syntenin mRNA and miR-139-3p levels were inversely correlated in clinical specimens (r = -0.6817, P = 0.0002). Overexpression of miR-139-3p in human glioma cell lines inhibited cell proliferation, migration, and invasion, and these effects were rescued by co-transfection with syntenin. Our results indicate that miR-139-3p plays a significant role in controlling behaviors associated with the malignant progression of gliomas, and we identify the miR-139-3p-syntenin axis as a potential therapeutic target for glioma. (C) 2018 Elsevier Inc. All rights reserved.