MicroRNA-936 promotes proliferation and invasion of gastric cancer cells by down-regulating FGF2 expression and activating P13K/Akt signaling pathway

摘要

OBJECTIVE: This study was designed to investigate whether microRNA-936 can be involved in the development of gastric cancer (GCa) by down-regulating FGF2 expression and activating the phosphatidylinositol 3-kinase/protein kinase B (P13K/Akt) signaling pathway. PATIENTS AND METHODS: Quantitative polymerase chain reaction (qPCR) was carried out to examine microRNA-936 and FGF2 levels in GCa tissue samples and adjacent normal ones, and further in GCa cell lines. After transfection of microRNA-936 inhibitor in GCa cell lines BGC and SGC, cell invasion, and proliferation abilities were evaluated by transwell and cell counting kit-8 (CCK-8) assays, respectively. In addition, the Dual-Luciferase reporting assay was conducted to verify the binding relationship between microRNA-936 and FGF2. After simultaneous transfection of microRNA-936 inhibitor and si-FGF2 in GCa cells, we detected the expression of FGF2/P13K/Akt by performing qPCR and Western blot experiments to further verify the regulation of microRNA-936 on FGF2 and PI3K/AKT pathway. RESULTS: QPCR detection revealed that microRNA-936 was remarkably up-regulated while FGF2 was conversely down-regulated in GCa tissue samples, indicating a negative correlation between the two. In addition, compared with normal gastric mucosal cells GES, microRNA-936 showed a significant increased expression in GCa cell lines. Meanwhile, down-regulation of microRNA-936 caused a marked reduction in invasive and proliferation ability of GCa cells. Dual-Luciferase reporting assay demonstrated a direct binding of microRNA-936 to FGF2. QPCR and Western blot showed that microRNA-936 can inhibit FGF2 expression and activate the PI3K/AKT pathway at the same time. Further studies found that silencing FGF2 induced an enhancement in cell proliferation and invasiveness, which could be reversed by simultaneous downregulation of microRNA-936. The above observations suggested that microRNA-936 may accelerate the progression of GCa by inhibiting FGF2 expression and activating the PI3K/AKT pathway. CONCLUSIONS: Overexpression of microRNA-936 can be conducive to the development of GCa, mainly through the down-regulation of FGF2 and activation of the P13K/Akt signaling pathway.