BACKGROUND: MicroRNAs [miRNAs] are key modulators of gene expression in Crohn's disease [CD] and may drive tissue-specific molecular alterations underlying CD susceptibility. In this study, we analysed differential miRNA expression between CD and healthy subjects across ileal and colonic tissues. METHODS: A cohort of CD and healthy control [HC] subjects was recruited and clinical data collected. Endoscopically quiescent CD [CDq] was defined as inactive or mild by the Simple Endoscopic Score for CD. Total RNA was extracted from endoscopic biopsies taken from the terminal ileum and sigmoid colon. miRNA expression was quantified using NanoString Technologies. Statistical significance was assessed across biopsy site and diagnosis per miRNA, and corrected for multiple testing. RESULTS: In total, 23 CDq and 38 HC subjects were enrolled; 112 samples were included in the analysis, 51 from the ileum and 61 from the colon. We found 47 miRNAs differentially expressed by biopsy site in healthy tissue. Nine miRNAs were differentially expressed across HC and CDq, accounting for biopsy location. One of these, miR-223-3p, showed age and sex effects. We identified miRNA expression driven by diagnosis targeting genes involved in chemokine and cytokine signalling. miR-31-5p expression was driven by location and may be a biomarker for location subtypes in CD. CONCLUSIONS: We identified differentially expressed miRNAs in healthy ileal and colonic tissues. We discovered spatial miRNA expression patterns in CD and HC, suggesting site-specific regulation in subjects with no or minimal intestinal inflammation. These miRNAs target genes involved in immunoregulatory processes, suggesting a functional, tissue-specific role in CD.
BACKGROUND: MicroRNAs [miRNAs] are key modulators of gene expression in Crohn's disease [CD] and may drive tissue-specific molecular alterations underlying CD susceptibility. In this study, we analysed differential miRNA expression between CD and healthy subjects across ileal and colonic tissues. METHODS: A cohort of CD and healthy control [HC] subjects was recruited and clinical data collected. Endoscopically quiescent CD [CDq] was defined as inactive or mild by the Simple Endoscopic Score for CD. Total RNA was extracted from endoscopic biopsies taken from the terminal ileum and sigmoid colon. miRNA expression was quantified using NanoString Technologies. Statistical significance was assessed across biopsy site and diagnosis per miRNA, and corrected for multiple testing. RESULTS: In total, 23 CDq and 38 HC subjects were enrolled; 112 samples were included in the analysis, 51 from the ileum and 61 from the colon. We found 47 miRNAs differentially expressed by biopsy site in healthy tissue. Nine miRNAs were differentially expressed across HC and CDq, accounting for biopsy location. One of these, miR-223-3p, showed age and sex effects. We identified miRNA expression driven by diagnosis targeting genes involved in chemokine and cytokine signalling. miR-31-5p expression was driven by location and may be a biomarker for location subtypes in CD. CONCLUSIONS: We identified differentially expressed miRNAs in healthy ileal and colonic tissues. We discovered spatial miRNA expression patterns in CD and HC, suggesting site-specific regulation in subjects with no or minimal intestinal inflammation. These miRNAs target genes involved in immunoregulatory processes, suggesting a functional, tissue-specific role in CD.
Authors: Francesco Fazi; Alessandro Rosa; Alessandro Fatica; Vania Gelmetti; Maria Laura De Marchis; Clara Nervi; Irene Bozzoni Journal: Cell Date: 2005-12-02 Impact factor: 41.582
Authors: Feng Wu; Natalie Jia Guo; Hongying Tian; Michael Marohn; Susan Gearhart; Theodore M Bayless; Steven R Brant; John H Kwon Journal: Inflamm Bowel Dis Date: 2010-09-01 Impact factor: 5.325
Authors: Feng Wu; Simin Zhang; Themistocles Dassopoulos; Mary L Harris; Theodore M Bayless; Stephen J Meltzer; Steven R Brant; John H Kwon Journal: Inflamm Bowel Dis Date: 2010-10 Impact factor: 5.325
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: Viola Neudecker; Moritz Haneklaus; Owen Jensen; Ludmila Khailova; Joanne C Masterson; Hazel Tye; Kathryn Biette; Paul Jedlicka; Kelley S Brodsky; Mark E Gerich; Matthias Mack; Avril A B Robertson; Matthew A Cooper; Glenn T Furuta; Charles A Dinarello; Luke A O'Neill; Holger K Eltzschig; Seth L Masters; Eóin N McNamee Journal: J Exp Med Date: 2017-05-09 Impact factor: 14.307
Authors: Luke Jostins; Stephan Ripke; Rinse K Weersma; Richard H Duerr; Dermot P McGovern; Ken Y Hui; James C Lee; L Philip Schumm; Yashoda Sharma; Carl A Anderson; Jonah Essers; Mitja Mitrovic; Kaida Ning; Isabelle Cleynen; Emilie Theatre; Sarah L Spain; Soumya Raychaudhuri; Philippe Goyette; Zhi Wei; Clara Abraham; Jean-Paul Achkar; Tariq Ahmad; Leila Amininejad; Ashwin N Ananthakrishnan; Vibeke Andersen; Jane M Andrews; Leonard Baidoo; Tobias Balschun; Peter A Bampton; Alain Bitton; Gabrielle Boucher; Stephan Brand; Carsten Büning; Ariella Cohain; Sven Cichon; Mauro D'Amato; Dirk De Jong; Kathy L Devaney; Marla Dubinsky; Cathryn Edwards; David Ellinghaus; Lynnette R Ferguson; Denis Franchimont; Karin Fransen; Richard Gearry; Michel Georges; Christian Gieger; Jürgen Glas; Talin Haritunians; Ailsa Hart; Chris Hawkey; Matija Hedl; Xinli Hu; Tom H Karlsen; Limas Kupcinskas; Subra Kugathasan; Anna Latiano; Debby Laukens; Ian C Lawrance; Charlie W Lees; Edouard Louis; Gillian Mahy; John Mansfield; Angharad R Morgan; Craig Mowat; William Newman; Orazio Palmieri; Cyriel Y Ponsioen; Uros Potocnik; Natalie J Prescott; Miguel Regueiro; Jerome I Rotter; Richard K Russell; Jeremy D Sanderson; Miquel Sans; Jack Satsangi; Stefan Schreiber; Lisa A Simms; Jurgita Sventoraityte; Stephan R Targan; Kent D Taylor; Mark Tremelling; Hein W Verspaget; Martine De Vos; Cisca Wijmenga; David C Wilson; Juliane Winkelmann; Ramnik J Xavier; Sebastian Zeissig; Bin Zhang; Clarence K Zhang; Hongyu Zhao; Mark S Silverberg; Vito Annese; Hakon Hakonarson; Steven R Brant; Graham Radford-Smith; Christopher G Mathew; John D Rioux; Eric E Schadt; Mark J Daly; Andre Franke; Miles Parkes; Severine Vermeire; Jeffrey C Barrett; Judy H Cho Journal: Nature Date: 2012-11-01 Impact factor: 49.962
Authors: Carolina Battistini; Rafael Ballan; Marcos Edgar Herkenhoff; Susana Marta Isay Saad; Jun Sun Journal: Int J Mol Sci Date: 2020-12-31 Impact factor: 5.923
Authors: Kanika Suri; Jason A Bubier; Michael V Wiles; Leonard D Shultz; Mansoor M Amiji; Vishnu Hosur Journal: Cells Date: 2021-08-26 Impact factor: 7.666
Authors: Reza Yarani; Ali Shojaeian; Oana Palasca; Nadezhda T Doncheva; Lars Juhl Jensen; Jan Gorodkin; Flemming Pociot Journal: Front Immunol Date: 2022-06-06 Impact factor: 8.786
Authors: Ranjit Pelia; Suresh Venkateswaran; Jason D Matthews; Yael Haberman; David J Cutler; Jeffrey S Hyams; Lee A Denson; Subra Kugathasan Journal: BMC Med Genomics Date: 2021-07-29 Impact factor: 3.063