Fig. 7
Therapeutic delivery of miR-4521 suppresses gastric carcinoma progression. a-d SGC7901 cells expressing a luciferase reporter (1 × 106 cells) were intraperitoneally injected into the nude mice. After 7 days, miR-4521 or control agomiR was delivered by intraperitoneal injection twice per week for 3 weeks (n = 5 mice/group) (a). At 30 days after cell injection, bioluminescence imaging and examination of intestinal, hepatic and splenic metastatic nodules showed that miR-4521 agomiR treatment significantly inhibited tumor metastasis (b, c). Arrows or circles indicate metastatic nodules. The body weight of mice is shown (d). Error bars represent SD, *P < 0.05; **P < 0.01. e Kaplan-Meier analysis of survival for mice treated with miR-4521 or control agomiR. f-g Mice were subcutaneously injected with 1 × 106 SGC7901 cells. Once tumors reached an average of 100 mm3 (14 days), the mice were treated with miR-4521 agomiR or control agomiR by intratumoral injection and closely monitored for tumor growth. The mice were sacrificed, and tumors were removed 32 days after inoculation. Error bars, SD (n = 5 mice/group). ***P < 0.001. h A schematic illustration of Hypoxia/ETS1/miR-4521/IGF2&FOXM1/AKT/Snai1 signaling pathway. Hypoxia downregulates miR-4521 through inducing ETS1. miR-4521 inactivates AKT/GSK3β/Snai1 signaling by suppressing IGF2 and FOXM1