Putative tumor suppressor miR‐145 inhibits colon cancer cell growth by targeting oncogene friend leukemia virus integration 1 gene

Abstract

BACKGROUND: Tumor suppressor microRNA miR‐145 is commonly down‐regulated in colon carcinoma tissues, but its specific role in tumors remains unknown. METHODS: In this study, the authors identified the Friend leukemia virus integration 1 gene (FLI1) as a novel target of miR‐145. FLI1 is involved in t(11;22)(q24:q12) reciprocal chromosomal translocation in Ewing sarcoma, and its expression appears to be associated with biologically more aggressive tumors. RESULTS: The authors demonstrated that miR‐145 targets a putative microRNA regulatory element in the 3′‐untranslated region (UTR) of FLI1, and its abundance is reversely associated with FLI1 expression in colon cancer tissues and cell lines. By using a luciferase/FLI1 3′‐UTR reporter system, they found that miR‐145 down‐regulated the reporter activity, and this down‐regulation was reversed by anti–miR‐145. Mutation of the miR‐145 microRNA regulatory element sequence in the FLI1 3′‐UTR abolished the activity of miR‐145. miR‐145 decreased FLI1 protein but not FLI1 mRNA, suggesting a mechanism of translational regulation. Furthermore, the authors demonstrated that miR‐145 inhibited cell proliferation and sensitized LS174T cells to 5‐fluorouracil–induced apoptosis. CONCLUSIONS: Taken together, these results suggest that miR‐145 functions as a tumor suppressor by down‐regulating oncogenic FLI1 in colon cancer. Cancer 2011. © 2010 American Cancer Society.