Objective: Aberrantly expressed microRNAs (miRs) may play critical roles in the regulation of tumorigenicity of various cancers. The present study was designed to investigate the expression, function and the underlying mechanism of miR-216b in hepatocellular carcinoma (HCC).
Materials and methods: The expression of miR-216b and FOXM1 in 24 paired HCC tissues and adjacent normal tissues was determined by Real-time PCR. The proliferative activity of HepG2 cells was determined by MTT assay. We analyzed cell cycle progression by flow cytometry, apoptosis by cell death enzyme-linked immunosorbent assay (ELISA) and cleaved-caspase-3 by western blot. Luciferase reporter assay was employed to verify whether FOXM1 serves as a target of miR-216b in vitro.
Results: The expression of miR-216b was significantly decreased in HCC tissues compared with that in adjacent normal tissues, whereas FOXM1 expression was increased. In addition, FOXM1 and miR-216b expression were inversely correlated in HCC tissues. Ectopic expression of miR-216b produced a suppressive effect on the growth of HepG2 cells and induced cell cycle arrest and apoptosis. We further demonstrated that miR-216b targets the 3' untranslated region (UTR) of FOXM1 directly to suppress the expression of FOXM1, and that suppression of FOXM1 produced the similar effects to miR-216b
Conclusions: These data suggest that down-regulation of miR-216b directly contributes to the up-regulation of FOXM1, which may confer the tumorigenicity of HCC cells. MiR-216b may serve as a potential therapeutic agent for HCC.