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2035O r i g i n a l r e s e a r c h open access to scientific and medical research Protein expression levels of Wnt1, E-cadherin, vimentin, β-cadherin, and N-cadherin were measured by Western blot. Cell proliferation, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound-healing assay, and Transwell assay, respectively. Results: Dual luciferase reporter gene results showed that Wnt1 is a direct target gene of miR-122 in both HepG2 and huh7 cell lines. Compared to miR-NC, anti-miR-NC, and miR-122 + Wnt1 groups, miR-122 expression was markedly higher in the miR-122 group and miR-122 + vector group, but was sharply decreased in anti-miR-122 group (both P,0.05), and the mRNA and protein levels of Wnt1, vimentin, β-cadherin, and N-cadherin decreased significantly; also E-cadherin increased, and cell proliferation, migration, and invasion decreased in the miR-122 group and miR-122 + vector group (all P,0.05), but the situation was totally reversed in the anti-miR-122 group (all P,0.05). Conclusion: Downregulation of miR-122 promoted proliferation, migration, and invasion of human HCC cells by targeting Wnt1 and regulating Wnt/β-catenin pathway which activated the EMT pathways.