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P046. Differential expression of microRNAs in inflamed colonic mucosa of patients with ulcerative colitis

J. Van der Goten1, I. Arijs1, L. Van Lommel2, W. Vanhove1, V. De Preter1, P. Rutgeerts1, F. Schuit2, S. Vermeire1

1Katholieke Universiteit Leuven, Department of Gastroenterology, Leuven, Belgium; 2Katholieke Universiteit Leuven, Gene Expression Unit, Department of Molecular Cell Biology, Leuven, Belgium

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by differential expression of genes involved in immune response, barrier integrity and tissue remodeling. MicroRNAs (miRNAs) are small non-coding RNAs which function as negative post-transcriptional regulators of gene expression. Recently, studies have shown their importance in regulating genes involved in immune function. In this study, microarray technology was used to investigate the altered miRNA expression in UC colonic mucosa.

Methods: Colonic mucosal biopsies were obtained during endoscopy from 10 active and 8 inactive UC patients, and 10 normal controls. Total RNA, including small RNA, was extracted and used to analyze the miRNA expression via Affymetrix GeneChip® miRNA 2.0 arrays. To assess gene expression, total RNA was isolated from biopsies and analyzed via Affymetrix GeneChip® Human Gene 1.0ST arrays. Data was analyzed with Bioconductor and Ingenuity Pathway Analysis (IPA) software. A false discovery rate <5% and >2-fold change was considered as significant.

Results: We identified 53 (26 up- and 27 downregulated) mature miRNAs and 1251 (844 up- and 407 downregulated) genes that were significantly different between active UC and controls. By IPA analysis, we observed an inverse relation between the increased miRNAs and 182 downregulated target mRNAs, and between the decreased miRNAs and 285 upregulated target mRNAs in active UC vs controls. The target mRNAs encode proteins that were predominantly involved in the biological functions: cellular movement (ERRFI1, FCGR2A, TNFRSF9), immune cell trafficking (FCGR2A, TNFRSF9), cell-to-cell signaling and interaction (FCGR2A, TNFRSF9), hematological system development and function (FCGR2A, IKZF3, PRDM1, TNFRSF9, TNFSF8), and cellular development (ERRFI1, FCGR2A, PRDM1, TNFRSF9, TNFSF8). In contrast, no significant miRNA expression differences were found between inactive UC and controls, while 31 miRNAs (14 up- and 17 downregulated) were significantly different between inactive and active UC, with 29/31 miRNAs common to the significant miRNAs between active UC and controls.

Conclusions: This study demonstrates that altered expression of miRNAs plays an important role in the expression of immune-related genes in inflamed UC mucosa. The absence of altered expression in inactive UC supports the potential role of miRNAs in immune activation in UC.