miR-21-5p and miR-146a-5a are deregulated in inflamed terminal ileum of treatment-naive pediatric patients with Crohn´s disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00111080" target="_blank" >RIV/00216224:14110/19:00111080 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.gastrojournal.org/article/S0016-5085(19)30264-1/fulltext?referrer=https%3A%2F%2Fwww.researchgate.net%2F" target="_blank" >https://www.gastrojournal.org/article/S0016-5085(19)30264-1/fulltext?referrer=https%3A%2F%2Fwww.researchgate.net%2F</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1053/j.gastro.2019.01.201" target="_blank" >10.1053/j.gastro.2019.01.201</a>

Jazyk výsledku

angličtina

Název v původním jazyce

miR-21-5p and miR-146a-5a are deregulated in inflamed terminal ileum of treatment-naive pediatric patients with Crohn´s disease

Popis výsledku v původním jazyce

Deregulation of intestinal microRNAs (miRNAs) have been reported in adult and, in the last years, also in pediatric patients with Crohn’s disease (CD). We performed a literature search and chose 4 miRNAs from five relevant studies as candidates for an independent validation (miR-21-5p, miR-31-5p, miR-146a-5p, miR-155-5p). The goal of this study was to verify deregulated expression of the candidate miRNAs in inflamed terminal ileum of treatment-naive pediatric patients with CD. Methods We collected formalin-fixed paraffin-embedded terminal ileum biopsies from treatment-naive pediatric patients with CD (n=20, median age 15 (range 10-18) years, 9 females, 11 males) and matched controls (pediatric patients undergoing endoscopy for suspicion of polyp or IBD; N=10). Total RNA enriched for small RNAs was isolated, and expression levels of candidate miRNAs were detected by use of quantitative real-time PCR. Levels of the candidate miRNA were normalized to match the levels of the reference miRNA, and statistically evaluated. Results We confirmed that miR-21-5p and miR-146a-5p have significantly higher expression in the inflamed mucosa of terminal ileum of CD patients in comparison to the terminal ileum of healthy controls (P=0.047, AUC=0.732, and P=0.046, AUC=0.768; respectively). We further developed a model based on the combination of miR-21-5p and miR-146a-5p expression, which enabled the identification of CD patients with sensitivity 86% and specificity 75% (AUC = 0.898). We were not able to validate deregulated expression of miR-31-5p and miR-155-5p in pediatric CD patients. Conclusions To our knowledge, this pilot study is the first one to evaluate the candidate miRNA expression levels exclusively in the terminal ileum of pediatric CD patients. We confirmed some of the previous observations (e.g. increased levels of inflammatory miR-21-5p and miR-146-5p), but surprisingly miR-155-5p and miR-31-5p, previously observed to be increased in the inflamed colonic biopsies, were not deregulated in terminal ileum of our pediatric CD patients. Further research is necessary to clarify the pathophysiological roles of these miRNAs in pediatric CD. This work was supported by the Ministry of Health of the Czech Republic, grant nr. 16-31314A, 16-31765A and RVO (FnBr, 65269705).

Název v anglickém jazyce

miR-21-5p and miR-146a-5a are deregulated in inflamed terminal ileum of treatment-naive pediatric patients with Crohn´s disease

Popis výsledku anglicky

Deregulation of intestinal microRNAs (miRNAs) have been reported in adult and, in the last years, also in pediatric patients with Crohn’s disease (CD). We performed a literature search and chose 4 miRNAs from five relevant studies as candidates for an independent validation (miR-21-5p, miR-31-5p, miR-146a-5p, miR-155-5p). The goal of this study was to verify deregulated expression of the candidate miRNAs in inflamed terminal ileum of treatment-naive pediatric patients with CD. Methods We collected formalin-fixed paraffin-embedded terminal ileum biopsies from treatment-naive pediatric patients with CD (n=20, median age 15 (range 10-18) years, 9 females, 11 males) and matched controls (pediatric patients undergoing endoscopy for suspicion of polyp or IBD; N=10). Total RNA enriched for small RNAs was isolated, and expression levels of candidate miRNAs were detected by use of quantitative real-time PCR. Levels of the candidate miRNA were normalized to match the levels of the reference miRNA, and statistically evaluated. Results We confirmed that miR-21-5p and miR-146a-5p have significantly higher expression in the inflamed mucosa of terminal ileum of CD patients in comparison to the terminal ileum of healthy controls (P=0.047, AUC=0.732, and P=0.046, AUC=0.768; respectively). We further developed a model based on the combination of miR-21-5p and miR-146a-5p expression, which enabled the identification of CD patients with sensitivity 86% and specificity 75% (AUC = 0.898). We were not able to validate deregulated expression of miR-31-5p and miR-155-5p in pediatric CD patients. Conclusions To our knowledge, this pilot study is the first one to evaluate the candidate miRNA expression levels exclusively in the terminal ileum of pediatric CD patients. We confirmed some of the previous observations (e.g. increased levels of inflammatory miR-21-5p and miR-146-5p), but surprisingly miR-155-5p and miR-31-5p, previously observed to be increased in the inflamed colonic biopsies, were not deregulated in terminal ileum of our pediatric CD patients. Further research is necessary to clarify the pathophysiological roles of these miRNAs in pediatric CD. This work was supported by the Ministry of Health of the Czech Republic, grant nr. 16-31314A, 16-31765A and RVO (FnBr, 65269705).

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30209 - Paediatrics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů