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. miR-26b is down regulated in several cancers and tumors and miR-26b directly targets the Lef-1 3'UTR and inhibits endogenous Lef-1 expression. We report that 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 expression is a potent inhibitor of colon cancer cell proliferation and significantly decreases LEF-1 expression. The LEF-1 regualted genes Cyclin D1 and c-Myc were indirectly repressed by miR-26b and this was consistent with decreased proliferation. miR-26b 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 miR-26b and LEF-1 expression. c-Myc expression is associated with multiple cancers and we propose that 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.

Repression of WT1-Mediated LEF1 Transcription by Mangiferin Governs β-Catenin-Independent Wnt Signalling Inactivation in Hepatocellular Carcinoma

“…A previous study stated that Wnt caused elevated LEF1 expression in a β-catenin-independent and LEF1-dependent manner [40], which supports our finding of β-catenin-independent LEF1 repression by mangiferin in HCC cells. LEF1 related signalling is a multi-targeted regulatory mechanism in which the aberrant activation of LEF1 results in cancer development by promoting processes such as invasion, proliferation, and self-renewal of cancer cells [28,41,42]. Our molecular finding that mangiferin represses LEF1 target genes accords with these previous studies, especially given our cellular finding mangiferin restricted HCC cell proliferation, migration, and chemotactic properties.…”

MicroRNA-133b is regulated by TAp63 while no gene mutation is present in colorectal cancer

“…Obviously, reduced expression of the transcription factor is not the only factor that downregulated the expression of miR-133b in CRC. To the best of our knowledge, different types of miRNAs have been identified as being downregulated in breast (27), gastric (28) and colon cancer (29). In addition, some of them were systematically proved to be closely associated with genetic polymorphisms and mutations (30).…”

Metformin and Colorectal Cancer Risk—Letter

“…miR-26b is associated with insulin resistance (3). miR-26b is a miRNA that has been shown to be involved in insulin sensitivity and cancer (3,4). miR-26b levels appear to be significantly lower in patients with insulin resistance in comparison with those without insulin resistance (3).…”

“…miR-26b levels appear to be significantly lower in patients with insulin resistance in comparison with those without insulin resistance (3). miR-26b is also downregulated in colorectal cancer (4). miR-26b has been shown to have a potent inhibitory effect on colon cancer cell proliferation (4).…”