Adam M Zahm1, Nicholas J Hand2, Daphne M Tsoucas3, Claire L Le Guen4, Robert N Baldassano5, Joshua R Friedman6. 1. The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: zahma@email.chop.edu. 2. The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: hand@email.chop.edu. 3. The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: dtsoucas@wharton.upenn.edu. 4. The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: leguencl@email.chop.edu. 5. The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: baldassano@email.chop.edu. 6. The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA. Electronic address: friedmaj@mail.med.upenn.edu.
Abstract
BACKGROUND AND AIMS: 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. CONCLUSION: 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.
BACKGROUND AND AIMS: 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 humanNOD2. CONCLUSION: 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: Joel R Pekow; Urszula Dougherty; Reba Mustafi; Hongyan Zhu; Masha Kocherginsky; David T Rubin; Stephen B Hanauer; John Hart; Eugene B Chang; Alessandro Fichera; Loren J Joseph; Marc Bissonnette Journal: Inflamm Bowel Dis Date: 2011-05-06 Impact factor: 5.325
Authors: Erik B Wendlandt; Joel W Graff; Theresa L Gioannini; Anton P McCaffrey; Mary E Wilson Journal: Innate Immun Date: 2012-04-20 Impact factor: 2.680
Authors: Feng Wu; Michelle Zikusoka; Anil Trindade; Themistocles Dassopoulos; Mary L Harris; Theodore M Bayless; Steven R Brant; Shukti Chakravarti; John H Kwon Journal: Gastroenterology Date: 2008-08-03 Impact factor: 22.682
Authors: Arie Levine; Anne Griffiths; James Markowitz; David C Wilson; Dan Turner; Richard K Russell; John Fell; Frank M Ruemmele; Thomas Walters; Mary Sherlock; Marla Dubinsky; Jeffrey S Hyams Journal: Inflamm Bowel Dis Date: 2010-11-08 Impact factor: 5.325
Authors: Jun Xie; Stefan L Ameres; Randall Friedline; Jui-Hung Hung; Yu Zhang; Qing Xie; Li Zhong; Qin Su; Ran He; Mengxin Li; Huapeng Li; Xin Mu; Hongwei Zhang; Jennifer A Broderick; Jason K Kim; Zhiping Weng; Terence R Flotte; Phillip D Zamore; Guangping Gao Journal: Nat Methods Date: 2012-03-04 Impact factor: 28.547
Authors: Ross John Porter; Caroline Andrews; Daniel Paul Brice; Scott Kenneth Durum; Mairi Hall McLean Journal: Inflamm Bowel Dis Date: 2018-09-15 Impact factor: 5.325
Authors: Adam M Zahm; Calies Menard-Katcher; Alain J Benitez; Daphne M Tsoucas; Claire L Le Guen; Nicholas J Hand; Joshua R Friedman Journal: Am J Physiol Gastrointest Liver Physiol Date: 2014-08-21 Impact factor: 4.052
Authors: HyunTaek Jung; Jae Seok Kim; Keum Hwa Lee; Kalthoum Tizaoui; Salvatore Terrazzino; Sarah Cargnin; Lee Smith; Ai Koyanagi; Louis Jacob; Han Li; Sung Hwi Hong; Dong Keon Yon; Seung Won Lee; Min Seo Kim; Paul Wasuwanich; Wikrom Karnsakul; Jae Il Shin; Andreas Kronbichler Journal: Int J Biol Sci Date: 2021-05-17 Impact factor: 6.580