(A) Hep3B cells stably transfected with lenti–miR-664, miR-485, and miR-495/EV or lenti-siRNA against these miRNAs or SC were injected into the left hepatic lobe, and mice were sacrificed after 45 days. The top row shows H&E staining of liver tumors, and tumor volume at the site of injection are shown below for each condition (*P < 0.05 vs. miR-485, miR-664 and EV; ^†P < 0.05 vs. EV; ^‡P < 0.05 vs. miR-485-3psi, miR-664si, and SC; ^§P < 0.05 vs. SC). Second row shows H&E staining of lung tissue and incidence of lung metastasis. Arrows point to lung metastasis. Third and fourth rows show immunohistochemistry for PCNA and MAT1A protein. Numbers below PCNA represent percentage of positive cells, *P < 0.01 vs. miR-485, miR-664 and EV; ^†P < 0.05 vs. EV; ^‡P < 0.05 vs. miR-485-3psi, miR-664si and SC; ^§P < 0.05 vs. SC. Original magnification, ×100 (first row); ×200 (second through fourth rows). (B) HepG2 cells capable of invasion and metastasis were injected into the left hepatic lobe as above, and lentiviral vectors containing miRNA siRNA or SC were injected into the spleen at the time of HepG2 cell injection. Two weeks later, lentiviral siRNA was injected into the tail vein, and this was repeated every 2 weeks until sacrifice at 8 weeks. H&E staining showing the effect of miR-495, miR-485-3p, and miR-664 siRNAs on tumor invasion and metastasis. Arrows point to tumor at the site of injection, and tumor volumes and invasion incidences are shown below each image. *P < 0.01 vs. scrambled siRNA (SC); ^†P < 0.05 vs. miR-485-3psi and miR-664si. Original magnification, ×100.