MicroRNA-26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 expression.

Abstract

microRNAs (miR) can act as oncogenes and tumor suppressors and several miRs are associated with cancer development and progression through the modulation of multiple cellular processes. miR26b is downregulated in several cancers and tumors and miR26b directly targets the lymphoid enhancer factor 1 (Lef1)3'UTR and inhibits endogenous Lef1 expression. We report that miR26b expression is associated with human colon cancer through the regulation of LEF1 expression in colon cancer cells. Analyses of multiple colon cancer cell lines revealed an inverse correlation between miR26b and LEF1 expression. Normal human colon cells express low levels of LEF1 and high levels of miR26b; however, human colon cancer cells have decreased miR26b expression and increased LEF1 expression. We demonstrate that miR26b expression is a potent inhibitor of colon cancer cell proliferation and significantly decreases LEF1 expression. The LEF1-regulated genes cyclin D1 and c-Myc were indirectly repressed by miR26b and this was consistent with decreased proliferation. miR26b overexpression in SW480 colon cancer cells also inhibited tumor growth in nude mice and this was due to decreased tumor growth and not apoptosis. Analyses of human colon cancer databases also demonstrated a link between miR26b and LEF1 expression. c-Myc expression is associated with multiple cancers and we propose that miR26b may act as a potential therapeutic agent in reducing cancer cell proliferation through repressing LEF1 activation of c-Myc and cyclin D1 expression.