Results　from　recent　studies　suggest　that　aberrant　microRNA　expression　is　common　in　numerous　cancers.　Although　miR-338-3p　has　been　implicated　in　hepatocellular　carcinoma,　its　role　in　gastric　cancer　is　unknown.　To　this　end,　we　report　that　miR-338-3p　is　downregulated　in　both　gastric　cancer　tissue　and　cell　lines.　Forced　expression　of　miR-338-3p　inhibited　cell　proliferation　and　clonogenicity　and　induced　a　G(1)-S　arrest　as　well　as　apoptosis　in　gastric　cancer　cells.　Furthermore,　P-Rex2a　(PREX2)　was　identified　as　a　direct　target　of　miR-338-3p,　and　silencing　P-Rex2a　resulted　in　the　same　biologic　effects　of　miR-338-3p　expression　in　gastric　cancer　cells.　Furthermore,　both　enforced　expression　of　miR-338-3p　or　silencing　of　P-Rex2a　resulted　in　activation　of　PTEN,　leading　to　a　decline　in　AKT　phosphorylation.　Also,　miR-338-3p　markedly　inhibited　the　in　vivo　tumorigenicity　in　a　nude　mouse　xenograft　model　system.　These　results　demonstrate　that　miR-338-3p　affects　gastric　cancer　progression　through　PTEN-AKT　signaling　by　targeting　P-Rex2a　in　gastric　cancer　cells,　which　posits　miR-338-3p　as　a　novel　strategy　for　gastric　cancer　treatment.　(C)2013　AACR.