Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon

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 human nCounter® platform and the TaqMan® low-density array platform, respectively. Significantly altered microRNAs were then 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 the 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 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 the targets of inflammatory bowel disease-associated microRNAs may lead to novel therapies.

Overexpression of miR-595 and miR-1246 in the Sera of Patients with Active Forms of Inflammatory Bowel Disease

“…Zahm et al identified CD-associated miRNAs in the sera of 6 adolescent children with active disease 32 and IBDassociated miRNAs in the sera of 18 UC and 11 CD pediatric patients. 33 MiR-142-5p, miR-143, miR-595, and miR-24, which were screened for were not identified. Iborra et al 34 compared miRNA expression levels in the sera of groups of 9 adult patients with active and inactive CD (mostly colonic) and UC to healthy subjects.…”

Chronic Administration of Δ 9 -Tetrahydrocannabinol Induces Intestinal Anti-Inflammatory MicroRNA Expression during Acute Simian Immunodeficiency Virus Infection of Rhesus Macaques

“…In a separate study involving atherosclerosis-susceptible endothelium, miR-10a expression was found to be downregulated and the expression of its predicted target HOXA1 was significantly upregulated (50). Likewise, miR-24 expression significantly increased in the inflamed colons of pediatric inflammatory bowel disease (IBD) patients, suggesting that the upregulation may be a host response to curtail inflammatory signaling (51). Similarly, IL-10 was reported to suppress production of proinflammatory cytokines such as TNF-␣, IL-6, and IL-12 by selectively inducing the upregulation of miR-187 (48).…”

“…Interestingly, at 60 days p.i., THC was found to selectively upregulate the expression of a group of 19 miRNAs, 6 of which (miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187) have been previously identified to target proinflammatory molecules such as cytokines and transcription factors (48)(49)(50)(51)(52)(53)(54). Among these, miR-10a was demonstrated to maintain intestinal homeostasis by targeting the proinflammatory cytokine IL-12/IL-23p40 in dendritic cells (DCs) (49).…”

“…Interestingly, all 19 miRNAs showed significantly elevated expression in the THC/SIV group compared to the VEH/SIV group (Table 4; see also Table S8 in the supplemental material). Among the these, miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187 have been previously reported to regulate inflammation (48)(49)(50)(51)(52)(53)(54). As shown in Fig.…”

A MicroRNA Signature in Pediatric Ulcerative Colitis

“…9 Very recently, a study identified a number of deregulated microRNAs in the rectal tissue of pediatric patients. 10 Our recent studies revealed that miR-124 is epigenetically regulated specifically in pediatric patients with active UC and this leads to increased STAT3 activity in the colonic tissue of these patients. 11 However, further investigation is needed to define the role and function of the microRNA-signature specific to pediatric UC patients.…”