Fig. 6

Circ-HuR suppresses gastric cancer progression by inhibiting CNBP transactivation in vivo. a Representative (left panel), in vivo growth curve (middle panel), and weight at the end points (right panel) of xenograft tumors formed by subcutaneous injection of AGS cells stably transfected with empty vector (mock) or CNBP, and those co-transfected with circ-Mock or circ-HuR into the dorsal flanks of nude mice (n = 5 for each group). b Representative images (left panel) and quantification (right panel) of immunohistochemical staining showing the expression of Ki-67 and CD31 within xenograft tumors formed by hypodermic injection of AGS cells stably transfected with mock or CNBP, and those co-transfected with circ-Mock or circ-HuR (n = 5 for each group). Scale bars: 50 μm. c-e Representative images (c), H&E staining (d, arrowheads), and quantification (e, left panel) of lung metastatic colonization and Kaplan-Meier curves (e, right panel) of nude mice treated with tail vein injection of AGS cells stably transfected with mock or CNBP, and those co-transfected with circ-Mock or circ-HuR (n = 5 for each group). Scale bar: 100 μm. f The mechanisms underlying circ-HuR-suppressed tumor progression: as a nuclear circRNA, circ-HuR interacts with CNBP to inhibit its binding to HuR promoter, resulting in down-regulation of HuR and suppression of gastric cancer progression. ANOVA analyzed the difference in (a, b, e). Log-rank test for survival comparison in (e). *P < 0.01 vs. mock+ circ-Mock. Data are shown as mean ± SEM (error bars)