title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Guo
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Guanxiang
authors.initials: G
authors.lastname: Qian
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
mesh_terms: 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
chemical_list: D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D051789:Proto-Oncogene Protein c-fli-1