MicroRNA-224 Promotes Cell Migration and Invasion by Targeting HOXA5 expression in Hepatocellular Carcinoma

MicroRNAs (miRNAs) are involved in the regulation of multiple cellular pathways and play a key role in the development and progression of tumor. Based on the cellular function of their targets, miRNAs play the role of oncogenes or tumor suppressor genes. Multiple studies have shown that abnormal expression of miRNAs has close relation with the incidence of HCC, but the mechanism of miRNAs in HCC still needs further research. In the present study, we showed that the overexpression of miR-224 can reduce the mRNA and protein expression of ADAM17 and HOXA5, the silencing of miR-224 can increase the protein expression of ADAM17 and HOXA5. Dual luciferase reporter assays showed that miR-224 can directly regulate the expression of ADAM17 and HOXA5. Importantly, we found that miR-224 positively regulates cell migration and invasion in HCC, miR-224 overexpression can promote the migration and invasion of BEL-7402 cell, and miR-224 silencing can suppress the migration and invasion of BEL-7402 cell. miR-224 overexpression can result in the redistribution of cell cycle, the cell percentage of S phase was increased significantly, the cell percentage of G1 phase was decreased significantly, and there is no noticeable change for the cell percentage of G2 phase. These results demonstrated that it may be exert the function of oncogenes in a particular link of cancer cell growth. In conclusion, these results suggest that miR-224 will become a promising biological target in the treatment strategy of hepatocellular carcinoma (HCC).