miR-22-3p regulates hepatocellular carcinoma invasion and proliferation through the Rap1/mTOR signaling pathway

Abstract

Objective Liver cancer is a deadly cancer worldwide. As important biomarkers, miRNAs play important roles in different tumors but the mechanism of miRNAs in hepatocellular carcinoma is unclear. This study aims at exploring the regulatory function and mechanisms linked to miR-22-3p in hepatoma.Methods A proper miR-22-3p evaluation has been perfomed in hepatocellular carcinoma cells. Different assays evaluated cell migration, invasion and expansion, including the CCK8, colony formation and transwell ones. The dual luciferase reporter analysis explored how miR-22-3p and Rap1B were related together. A xenograft model in nude mice was also developed.Results Low miR-22-3p levels were poorly prognostic in patients with hepatoma. The miR-22-3p expression was downregulated in hepatocellular carcinoma tissues. In hepatocellular carcinoma cells, silencing miR-22-3p significantly favored cell expansion, migration and invasion, whereas miR22-3p overexpression determined opposite findings. The miR-22-3p bound to Rap1B 3’ UTR regulated the expression of Rap1B, thereby further activating its downstream signaling molecules.Conclusion In hepatocellular carcinoma, the miR-22-3p influenced cell expansion, invasion and migration through the novel target Rap1B and the mTOR pathway.