title: MicroRNA-155 is involved in the pathogenesis of ulcerative colitis by targeting FOXO3a.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are important posttranscriptional regulators of gene expression. The precise role of miRNAs in ulcerative colitis (UC) is not completely understood. The purpose of this study was to identify miRNAs that are induced in patients with active UC and to assess the effect of miR-155 on improving intestinal inflammation.
  
  
  METHODS
  The miRNA profiles in patients with active UC (n = 20) and healthy subjects (n = 16) were examined using miRNA microarrays. miR-155 upregulation was confirmed by quantitative RT-PCR. Regulation of the target gene FOXO3a expression by miR-155 was assessed using luciferase reporter construct assays and miR-155 mimic or inhibitor transfections. The effects of FOXO3a or miR-155 on IκBα or IL-8 were detected by Western blot or enzyme-linked immunosorbent assay in HT29 cells, respectively.
  
  
  RESULTS
  We identified 68 miRNAs that were differentially expressed (33 upregulated and 35 downregulated) in patients with active UC compared with healthy controls. One of the upregulated miRNAs in the UC tissue was miR-155 (1.22-fold, P < 0.03), which plays a key role in the regulation of inflammatory pathways. In patients with active UC, miR-155 was significantly upregulated, and the expression of FOXO3a dramatically decreased. Luciferase reporter assays demonstrated that miR-155 directly targets FOXO3a and affects the protein expression of FOXO3a in HT29 cells. Moreover, silenced FOXO3a and the overexpression of miR-155 increased the levels of IL-8 in TNF-α-treated HT29 cells by suppressing the inhibitory IκBα.
  
  
  CONCLUSIONS
  miR-155 appears to play a role in the intestinal inflammation of patients with active UC by downregulating the expression of FOXO3a. This process may activate the nuclear factor kappa B signaling pathway.
authors.affiliation: *Department of Gastroenterology and Hepatology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China; and †Institute of Digestive Diseases, Chinese PLA General Hospital, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Min
authors.forename: Lihua
authors.initials: L
authors.lastname: Peng
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D020672:I-kappa B Proteins; D016209:Interleukin-8; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha