Nóra Judit Béres1, Zoltán Kiss1, Zsófia Sztupinszki1, Gábor Lendvai2, András Arató1, Erna Sziksz3, Ádám Vannay3, Attila J Szabó3, Katalin Eszter Müller1, Áron Cseh1, Kriszta Boros1, Gábor Veres4. 1. 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary. 2. MTA-SE Tumor Progression Research Group, Budapest, Hungary. 3. 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary; MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary. 4. 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary; MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary. Electronic address: veres.gabor@med.semmelweis-univ.hu.
Abstract
INTRODUCTION: MicroRNAs (miRs) came recently into focus as promising novel research targets offering new insights into the pathogenesis of inflammatory bowel diseases (IBD). AIMS: The aim of our study was to identify a pediatric IBD (pIBD) characteristic miR profile serving as potential Crohn's disease (CD) and ulcerative colitis (UC) specific diagnostic pattern and to further analyze the related target genes. METHODS: Small RNA sequencing was performed on inflamed and intact colonic biopsies of CD, and control patients. Selected miRs were further investigated by RT-PCR, complemented with an UC group, in order to address the differential diagnostic potential of miRs in the two IBD subtypes. To analyze network connection of differentially expressed miRs and their target genes MiRTarBase database and previous transcriptome sequencing data from pediatric patient groups were used. RESULTS: Sequencing analysis identified 170 miRs with altered expression. RT-PCR analysis revealed altered expression of miR-31, -125a, -142-3p, and -146a discriminating between the inflamed mucosa of CD and UC. In the intact mucosa of CD patients the expression of miR-18a, -20a, -21, -31, -99a, -99b, -100, -125a, -126, -142-5p, -146a, -185, -204, -221, and -223 was elevated compared to the controls. The expression of miR-20a, -204 and -221 was elevated exclusively in the intact region of CD patients compared to the controls. Enrichment analysis identified main IBD-related functional groups. CONCLUSIONS: We demonstrated a characteristic colonic miR pattern in pIBD that could facilitate deeper understanding of the pathomechanism of IBD and may serve as a diagnostic tool.
INTRODUCTION: MicroRNAs (miRs) came recently into focus as promising novel research targets offering new insights into the pathogenesis of inflammatory bowel diseases (IBD). AIMS: The aim of our study was to identify a pediatric IBD (pIBD) characteristic miR profile serving as potential Crohn's disease (CD) and ulcerative colitis (UC) specific diagnostic pattern and to further analyze the related target genes. METHODS: Small RNA sequencing was performed on inflamed and intact colonic biopsies of CD, and control patients. Selected miRs were further investigated by RT-PCR, complemented with an UC group, in order to address the differential diagnostic potential of miRs in the two IBD subtypes. To analyze network connection of differentially expressed miRs and their target genes MiRTarBase database and previous transcriptome sequencing data from pediatric patient groups were used. RESULTS: Sequencing analysis identified 170 miRs with altered expression. RT-PCR analysis revealed altered expression of miR-31, -125a, -142-3p, and -146a discriminating between the inflamed mucosa of CD and UC. In the intact mucosa of CDpatients the expression of miR-18a, -20a, -21, -31, -99a, -99b, -100, -125a, -126, -142-5p, -146a, -185, -204, -221, and -223 was elevated compared to the controls. The expression of miR-20a, -204 and -221 was elevated exclusively in the intact region of CDpatients compared to the controls. Enrichment analysis identified main IBD-related functional groups. CONCLUSIONS: We demonstrated a characteristic colonic miR pattern in pIBD that could facilitate deeper understanding of the pathomechanism of IBD and may serve as a diagnostic tool.
Authors: Benjamin P Keith; Jasmine B Barrow; Takahiko Toyonaga; Nevzat Kazgan; Michelle Hoffner O'Connor; Neil D Shah; Matthew S Schaner; Elisabeth A Wolber; Omar K Trad; Greg R Gipson; Wendy A Pitman; Matthew Kanke; Shruti J Saxena; Nicole Chaumont; Timothy S Sadiq; Mark J Koruda; Paul A Cotney; Nancy Allbritton; Dimitri G Trembath; Francisco Sylvester; Terrence S Furey; Praveen Sethupathy; Shehzad Z Sheikh Journal: JCI Insight Date: 2018-10-04
Authors: Timothy Sadlon; Cheryl Y Brown; Veronika Bandara; Christopher M Hope; John E Schjenken; Stephen M Pederson; James Breen; Alistair Forrest; Marc Beyer; Sarah Robertson; Simon C Barry Journal: Clin Transl Immunology Date: 2018-02-27