title: Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon.
abstract: OBJECTIVE
  Changes in intestinal microRNAs have been reported in adult patients with ulcerative colitis or Crohn's disease. The goal of this study was to identify changes in microRNA expression associated with colitis in children with inflammatory bowel disease.
  
  
  METHODS
  Rectal mucosal biopsies (n = 50) and blood samples (n = 47) were collected from patients with known or suspected inflammatory bowel disease undergoing endoscopy. Rectal and serum microRNA levels were profiled using the nCounter platform and the TaqMan low-density array platform, respectively. Significantly altered microRNAs were validated in independent sample sets via quantitative RT-PCR. In vitro luciferase reporter assays were performed in the human colorectal Caco-2 cell line to determine the effect of miR-192 on NOD2 expression.
  
  
  RESULTS
  Profiling of rectal RNA identified 21 microRNAs significantly altered between control, UC, and colonic CD sample groups. Nine of the ten microRNAs selected for validation were confirmed as significantly changed. Rectal miR-24 was increased 1.47-fold in UC compared to CD samples (p = 0.0052) and was the only microRNA altered between IBD subtypes. Three colitis-associated microRNAs were significantly altered in sera of disease patients and displayed diagnostic utility. However, no serum microRNAs were found to distinguish ulcerative colitis from Crohn's colitis. Finally, miR-192 inhibition did not affect luciferase reporter activity, suggesting that miR-192 does not regulate human NOD2.
  
  
  CONCLUSIONS
  This study has demonstrated that rectal and serum microRNAs are perturbed in pediatric inflammatory bowel disease. Future studies identifying targets of inflammatory bowel disease-associated microRNAs may lead to novel therapies.
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: zahma@email.chop.edu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zahm
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: hand@email.chop.edu.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hand
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: dtsoucas@wharton.upenn.edu.
authors.forename: Daphne M
authors.initials: DM
authors.lastname: Tsoucas
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: leguencl@email.chop.edu.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Le Guen
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: baldassano@email.chop.edu.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: friedmaj@mail.med.upenn.edu.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002460:Cell Line; D002648:Child; D003113:Colonoscopy; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000378:metabolism* / Q000473:pathology
chemical_list: D035683:MicroRNAs
keywords: Circulating microRNA; Crohn's disease; Inflammatory bowel disease; MicroRNA; Serum microRNA; Ulcerative colitis