MicroRNA-218 and microRNA-520a inhibit cell proliferation by downregulating E2F2 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer type worldwide and the third leading cause of cancer-associated mortality. To date, its pathogenesis has remained poorly understood. Previous studies have demonstrated that deregulated microRNA (miR) participates in hepatocarcinogenesis. In the present study, miR-218 and miR-520a were observed to be downregulated in human HCC cells relative to normal hepatic cells. Overexpression of miR-218 or miR-520a inhibited cell proliferation and induced cell cycle arrest at the G(0)/G(1) phase checkpoint. Furthermore, a dual-luciferase reporter assay identified that E2F2 was a novel direct target of miR-218 but not miR-520a in HCC. In addition, miR-218 and miR-520a were observed to negatively regulate E2F2 mRNA and protein levels. This suggested that miR-218 regulated the expression of E2F2 via directly binding to its 3-untranslated region, whereas miR-520a affected E2F2 expression indirectly. In conclusion, these results indicated that miR-218 and miR-520a are crucial in the development of HCC via the inhibition of cell proliferation and cycle progression by downregulating E2F2.