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Molecular medicine reports

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


PMID 25816091

Abstract

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 G0/G1 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.