期刊
CANCER
卷 117, 期 1, 页码 86-95出版社
WILEY
DOI: 10.1002/cncr.25522
关键词
miR-145; FLI1; microRNA; colon cancer; cell proliferation; tumor suppressor
类别
资金
- National Key Program for Basic Research of China [2010CB529902, 2010CB834201]
- National Natural Science Foundation of China [30973663, 10935009]
- Science and Technology Commission of Shanghai [08ZR1412500, 10JC1409100]
- Shanghai Leading Academic Discipline Project [S30205]
- Shanghai Municipal Education Commission [jdy08054, 09ZZ110]
- NIH [1R43 CA103553-01]
- Department of Defense [W81XWH-04-1-0597]
- NATIONAL CANCER INSTITUTE [R43CA103553] Funding Source: NIH RePORTER
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;117:86-95. (C) 2010 American Cancer Society.
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