Fig. 7

Re-overexpression diminished the suppressive effects of miR-590-5p in GC. a FGF18 mRNA was restored in FGF18 re-overexpressed AGS and MKN28 cells (*, P < 0.05; **, P < 0.001). b FGF18 re-overexpression promoted growth in the miR-590-5p treated cells (**, Negative control + Empty vector vs. miR-590-5p + Empty vector, P < 0.001; ##, miR-590-5p + Empty vector vs. miR-590-5p + FGF18, P < 0.001). c Monolayer colony formation ability of AGS and MKN28 cells, which were transfected with miR-590-5p, were rescued by FGF18 re-overexpression (**, P < 0.001). d The invasive ability was significantly raised in FGF18 re-overexpressed cells compared with miR-590-5p treated cells (**, P < 0.001). SDs were achieved from triplicate experiments. e FGF18 re-overexpression in MGC-803 cells formed bigger xenografts compared with miR-590-5p transfection group (**, P < 0.001). f Schematic figure summarized all the study. In normal gastric epithelium cells, miR-590-5p suppresses FGF18 expression and blocks FGF18 signaling. The ATM signaling is normally activated, which in turn induces DNA damage repair, cell cycle arrest and apoptosis. In GC cells, silenced miR-590-5p fails to inhibit FGF18 expression. Thus the activated FGF18 axis triggers MEK-ERK and Smad2/3 signalings through FGFR, which promotes downstream expression and causes aberrant proliferation and invasion