title: Overexpression of miR-595 and miR-1246 in the sera of patients with active forms of inflammatory bowel disease.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are dysregulated in the inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), which arise due to dysfunctional host-microbe interactions and impairment of the barrier function of the intestine. Here, we sought to determine whether circulating miRNAs are biomarkers of active colonic CD and UC and can provide insights into disease pathogenesis. Comparison was made with serum miRNAs in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Total serum RNA from patients with colonic CD, UC, and RA, and normal healthy adults was screened for disease-associated miRNAs by microarray analysis, with subsequent validation by quantitative reverse-transcription polymerase chain reaction. MiRNA targets were identified by luciferase reporter assays.
  
  
  RESULTS
  MiR-595 and miR-1246 were significantly upregulated in the sera of active colonic CD, UC, and RA patients, compared with healthy subjects; and in active colonic CD and UC compared with inactive disease. Luciferase reporter assays indicated that miR-595 inhibits the expression of neural cell adhesion molecule-1 and fibroblast growth factor receptor 2.
  
  
  CONCLUSIONS
  Serum miR-595 and miR-1246 are biomarkers of active CD, UC, and RA. These findings gain significance from reports that miR-595 impairs epithelial tight junctions, whereas miR-1246 indirectly activates the proinflammatory nuclear factor of activated T cells. miR-595 targets the cell adhesion molecule neural cell adhesion molecule-1, and fibroblast growth factor receptor 2, which plays a key role in the differentiation, protection, and repair of colonic epithelium, and maintenance of tight junctions. miR-595 and miR-1246 warrant testing as potential targets for therapeutic intervention in the treatment of inflammatory bowel disease.
authors: Departments of *Molecular Medicine and Pathology, and †Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; and ‡Department of Rheumatology, Auckland District Health Board, Auckland, New Zealand.
authors: Geoffrey W
authors: GW
authors: Krissansen
authors: Yi
authors: Y
authors: Yang
authors: Fiona M
authors: FM
authors: McQueen
authors: Euphemia
authors: E
authors: Leung
authors: Deborah
authors: D
authors: Peek
authors: Yih Chih
authors: YC
authors: Chan
authors: Cristin
authors: C
authors: Print
authors: Nicola
authors: N
authors: Dalbeth
authors: Megan
authors: M
authors: Williams
authors: Alan G
authors: AG
authors: Fraser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis*; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000097:blood / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; C577700:MIRN1246 microRNA, human; C579843:MIRN596 microRNA, human; D035683:MicroRNAs; C522918:NCAM1 protein, human; D012333:RNA, Messenger; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2