MicroRNA‐26b Represses Colon Cancer Cell Proliferation by Inhibiting Lymphoid Enhancer Factor 1 (LEF‐1) Expression

Abstract

microRNAs can act as oncogenes and tumor suppressors and miR‐26b is down regulated in several cancers and tumors. We have previously reported that miR‐26b directly targets the Lef‐1 3'UTR and inhibits endogenous Lef‐1 expression. miR‐26b expression is associated with human colon cancer through the regulation of LEF‐1 expression in colon cancer cells. Analyses of multiple colon cancer cell lines revealed an inverse correlation between miR‐26b and LEF‐1 expression. Normal human colon cells express low levels of LEF‐1 and high levels of miR‐26b, however human colon cancer cells have decreased miR‐26b expression and increased LEF‐1 expression. We demonstrate that miR‐26b has a potent inhibitory effect on colon cancer cell proliferation. Endogenous LEF‐1 expression was significantly decreased by miR‐26b over expression. The Wnt/β‐catenin target genes cyclin D1 and c‐MYC were also repressed resulting in reduced cell proliferation. Furthermore, miR‐26b inhibits the growth of SW480 colon cancer cells in mice xenograft experiments. c‐MYC expression is associated with multiple cancers and we propose miR‐26b may act as a potential therapeutic agent in reducing cancer cell proliferation through repressing LEF‐1 activation of c‐MYC and cyclin D1 expression.