Fig. 8. Combined effects of circUBAP2 and miR-4756 on tumor growth and lung metastasis in the orthotopically implanted tumor model in BALBc nude mice.

A, C The orthotopic implantation tumor model was conducted by injecting Huh-7 cells coinfected with sh-NC/sh-circUBAP2 and anti-NC/anti-miR-4756 lentivirus into the left liver lobe of mice. After 5 weeks, anesthetized mice were sacrificed and livers and lungs were collected for further experiments. B Tumor numbers in mice livers from different groups were counted. D Lung metastatic nodules in mice from different groups were counted. E The histopathological characteristics of mice livers and lungs were evaluated by H&E staining. The protein content and distribution of IFIT1/3 in mice liver tumors were examined by IHC staining. F The expression levels of circUBAP2 and miR-4756 in mice livers from different groups were examined by qRT-PCR. G The protein levels of IFIT1/3, Vimentin, and Twist in mice livers tumors from different groups were examined by Immunoblotting. H A schematic graph of the mechanism. CXCL11 acts as a key mediator integrating CAFs and CAFs-cohabitating HCC cells, and also work as an extracellular remodeler promoting HCC migration and metastasis through the activation of circUBAP2/miR-4756/IFIT1/3 in tumor cells. **P < 0.01, compared with the sh-NC + anti-NC group; ^##P < 0.01, compared with the sh-circUBAP2 + anti-miR-4756 group.