MicroRNA‐195 Suppresses Angiogenesis and Metastasis of Hepatocellular Carcinoma by Inhibiting the Expression of VEGF, VAV2, and CDC42

摘要: Hepatocellular carcinoma (HCC) is characterized by active angiogenesis and metastasis, which account for rapid recurrence poor survival. There frequent down-regulation of miR-195 expression in HCC tissues. In this study, the role metastasis was investigated with vitro capillary tube formation transwell assays, vivo orthotopic xenograft mouse models, human specimens. Reduction tissues significantly associated increased angiogenesis, worse recurrence-free Both gain-of-function loss-of-function studies models revealed that not only suppressed ability cells to promote migration endothelial but also directly repressed abilities migrate invade extracellular matrix gel. Based on we found induced dramatically reduced microvessel densities tumors both intrahepatic pulmonary metastasis. Subsequent investigations disclosed inhibited proangiogenic factor vascular growth (VEGF) prometastatic factors VAV2 CDC42. Knockdown these target molecules phenocopied effects restoration, whereas overexpression targets antagonized function miR-195. Furthermore, resulted enhanced VEGF levels tumor microenvironment, subsequently activated receptor 2 signaling thereby promoted angiogenesis. Additionally, led increases CDC42 expression, stimulated VAV2/Rac1/CDC42 lamellipodia facilitated cells. Conclusion: deregulation contributes HCC. The restoration may be a promising strategy therapy. (Hepatology 2013;58:642-653)