Recent evidence suggests that microRNAs play important roles in the negative post-transcriptional regulators with altered expression levels found in gastric cancer (GC). Therefore, we employed explore the anti-cancer miRNA and the potential mechanisms by which miRNAs modulate GC progression. We have predicted GC miRNA expression data sets in TargetScan. miR-5590-3p is higher in adjacent nonmalignant tissue than in cancer tissue in 42 pairs of GC tissues. Functional assays, CCK-8 and colony formation assay, were used to determine the Anti-cancer role of miR-5590-3p in human GC progression. In addition, Ago2-based RIP and dual-luciferase reporter assay were conducted to study the miR-5590-3p as a direct target of DDX5. Next, Xenograft nude mouse models were used to determine the role of miR-5590-3p in GC tumorigenicity in vivo. Upregulation of miR-5590-3p suppressed GC cell, proliferation, whereas downregulation of miR-5590-3p promoted GC proliferation in vitro. Furthermore, we identified DDX5 as a direct target of miR-5590-3p, and that the biological function of miR-5590-3p during GC progression in vitro and in vivo is through the DDX5/AKT/m-TOR pathway and downstream cyclinDl and CDK2 expression. Finally, we confirmed the effect of miR-5590-3p directly targeting DDX5 on the development of gastric cancer through salvage experiments in vivo and in vitro. (C) 2018 Elsevier Inc. All rights reserved.