title: Novel MicroRNA Signature to Differentiate Ulcerative Colitis from Crohn Disease: A Genome-Wide Study Using Next Generation Sequencing.
abstract: The diagnosis of ulcerative colitis (UC) or Crohn disease (CD) can be challenging given the overlapping features. Knowledge of microRNAs in IBD has expanded recently and supports that microRNAs play an important role. This study aimed to identify novel microRNA biomarkers through comprehensive genome-wide sequencing to distinguish UC from CD.
  
  
  
  Illumina next generation sequencing was performed on nondysplastic fresh-frozen colonic mucosa of the distal-most colectomy from 19 patients (10 UC and 9 CD) and 18 patients with diverticular disease serving as controls.
  
  
  
  USeq software package identified 44 microRNAs with altered expression (fold change ≥2 and false discovery rate ≤0.10) compared to controls. Among them, a panel of 11 microRNAs was aberrantly expressed between UC and CD. qRT-PCR validation assays performed on frozen tissue from additional samples of UC (n=20) and CD (n=10) confirmed specific differential expression of miR-147b, miR-194-2, miR-383, miR-615 and miR-1826 (P<0.05). In addition, pathway analysis identified target genes of epithelial adhesion junction, integrin, glycolysis and cell cycle that involve in signaling pathways of TGF-β, STAT3, IL-8 and PI3L/AKT/mTOR.
  
  
  
  Identification of differentially expressed microRNAs in UC and CD supports the hypothesis that UC and CD are regulated by distinct pathophysiologic mechanisms. MicroRNA panels show promise as diagnostic biomarkers for the subtyping of inflammatory bowel disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Lin
authors.forename: Xinjun
authors.initials: X
authors.lastname: Zhang
authors.forename: Zijin
authors.initials: Z
authors.lastname: Zhao
authors.forename: Noah C
authors.initials: NC
authors.lastname: Welker
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000235:genetics*; D003106:Colon / Q000166:cytology / Q000473:pathology; D003424:Crohn Disease / Q000175:diagnosis* / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs