Fig. 5
Downregulation of EV secretion via let-7a/SNAP23 axis inhibits tumor growth. a Cell invasion by transwell assay in SW620 cells overexpressing vector and SNAP23 treated with ctrl or let-7a mimic. Scale bar, 200 μM. Original magnification: 200×. b Cell invasion in SW480 sh-NT and sh-SNAP23 treated with ctrl or let-7a inhibitor. Scale bar, 200 μM. Original magnification: 200×. c Upon SW480 sh-NT and sh-SNAP23 tumor xenografts reaching a volume of ~ 30 mm3, 3 μg of EVs derived from sh-NT SW480 cells or PBS were intravenously injected into NSG mice through the tail vein twice a week. Tumor sizes were measured twice weekly. d Tumor weights were determined at the experimental end-point (4 weeks). e Representative images of xenograft tumors suggested that knockdown of SNAP23 significantly reduced tumor sizes and weights. However, an injection of EVs from CRC cells partially rescued tumor sizes and weights in sh-SNAP23 groups. f, h Representative images of xenograft tumors that were subjected to PCNA and Ki67 staining. Scale bar, 40 μM. g, i The numbers of positive cells/high power field (HPF) were shown in groups. j Representative IHC for SNAP23 in CRC tumor tissue (T) compared with adjacent normal tissue (NT). Scale bar, 100 μM. IHC staining scores (k) and percentage of SNAP23 levels (l) from CRC patients (n = 31) showed that SNAP23 expression in CRC groups (T) was higher than in normal groups (NT). Data represent the mean ± SEM of at least two independent experiments. *p < 0.05, **p < 0.01 and ***p < 0.001