title: Integrated miRNA and mRNA expression profiling in inflamed colon of patients with ulcerative colitis.
abstract: BACKGROUND
  Ulcerative colitis (UC) is associated with differential colonic expression of genes involved in immune response (e.g. IL8) and barrier integrity (e.g. cadherins). MicroRNAs (miRNAs) are regulators of gene expression and are involved in various immune-related diseases. In this study, we investigated (1) if miRNA expression in UC mucosa is altered and (2) if any of these changes correlate with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their target mRNA.
  
  
  METHODS
  Colonic mucosal biopsies were obtained from 17 UC (10 active and 7 inactive) patients and 10 normal controls. Total RNA was used to analyze miRNA and mRNA expression via Affymetrix miRNA 2.0 and Affymetrix Human Gene 1.0ST arrays, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of IL8 and CDH11 expression by hsa-miR-200c-3p was determined by luciferase reporter assays.
  
  
  RESULTS
  When comparing active UC patients vs. controls, 51 miRNAs and 1543 gene probe sets gave significantly different signals. In contrast, in inactive UC vs. controls, no significant miRNA expression differences were found while 155 gene probe sets had significantly different signals. We then identified potential target genes of the significantly dysregulated miRNAs and genes in active UC vs. controls and found a highly significant inverse correlation between hsa-miR-200c-3p and IL8, an inflammatory marker, and between hsa-miR-200c-3p and CDH11, a gene related to intestinal epithelial barrier function. We could demonstrate that hsa-miR-200c-3p directly regulates IL8 and CDH11 expression.
  
  
  CONCLUSIONS
  Differential expression of immune- and barrier-related genes in inflamed UC mucosa may be influenced by altered expression of miRNAs. Integrated analysis of miRNA and mRNA expression profiles revealed hsa-miR-200c-3p for use of miRNA mimics as therapeutics.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van der Goten
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Wiebe
authors.initials: W
authors.lastname: Vanhove
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Machiels
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Willem-Jan
authors.initials: WJ
authors.lastname: Wollants
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Vicky
authors.initials: V
authors.lastname: De Preter
authors.affiliation: Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arijs
mesh_terms: D001483:Base Sequence; D001706:Biopsy; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D015820:Cadherins; D016209:Interleukin-8; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C086960:osteoblast cadherin; D008156:Luciferases