Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene.
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.
Zhang
Jianjun
J
Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Guo
Haiyan
H
Zhang
He
H
Wang
Haibo
H
Qian
Guanxiang
G
Fan
Xianqun
X
Hoffman
Andrew R
AR
Hu
Ji-Fan
JF
Ge
Shengfang
S
D020413:3' Untranslated Regions; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D005786:Gene Expression Regulation; D018390:Gene Targeting; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid
D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D051789:Proto-Oncogene Protein c-fli-1