Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease

Abstract

BACKGROUND: Evidence suggests the central role of tumor necrosis factor (TNF)-alpha in the pathomechanism of inflammatory bowel disease (IBD); however, its effect on epigenetic factors, including small non-coding microRNAs (miRs), is less known. Our present aim was the comparative investigation of the expression of TNF-alpha and immune response-related miRs in children with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Fresh-frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) biopsies were used to analyze the expression of miR-146a, -155, -122, and TNF-alpha by real-time reverse transcription polymerase chain reaction in macroscopically inflamed (CD: 12 FFPE and 24 FF; UC: 10 FF) and intact (CD: 12 FFPE; 14 FF) colonic biopsies of children with IBD and controls (16 FFPE; 23 FF). The expression of miR-146a, -155, and -122 was also determined in TNF-alpha-treated HT-29 colonic epithelial cells. RESULTS: Increased expression of TNF-alpha was observed in the colonic mucosa of children with CD and UC in comparison with controls. Expression of miR-146a and -155 was higher in the inflamed mucosa of children with CD and UC than in the intact mucosa. Expression of miR-122 elevated in the macroscopically intact colonic regions of CD compared with controls and patients with UC. In HT-29 cells, TNF-alpha treatment increased the expression of miR-146a and -155, but not that of miR-122. CONCLUSIONS: Our results showed altered expression of miR-146a, -155, and -122 in the colonic mucosa of children with IBD and in TNF-alpha-treated colonic epithelial cells. Our data suggest the TNF-alpha-related involvement of these miRs in the pathogenesis of IBD.