Alterations in microRNA expression profiles in inflamed and non-inflamed ascending colon mucosae of patients with active Crohn's disease

Abstract

Background and aims The miRNA expression profiles of the terminal ileum, sigmoid colon, and rectal mucosa of adult patients with active Crohn';s disease (CD) have been previously reported. The purpose of this study was to identify dysregulated miRNAs in the mucosa of the ascending colon. Methods Biopsy tissue samples were taken from the mucosae of inflammatory (iCD) or non-inflammatory (niCD) areas of the ascending colons of adult patients with active CD. miRNA and mRNA expression profiles were detected using microarray analyses. miRNAs and mRNAs demonstrating significant differences were validated via quantitative real-time PCR (qRT-PCR). Luciferase reporter genes were used to measure two miRNAs inhibition of potential target genes in human 293T cells in vitro. Results Compared with the HC group, the ascending colon miRNA expression profiles revealed that 43 miRNAs were significantly up-regulated and 35 were down-regulated in the iCD group. The mRNA expression profiles indicated that 3,370 transcripts were significantly differentially expressed in the ascending colon, with 2169 up-regulated and 1201 down-regulated mRNAs in the iCD group, and only 20 miRNAs demonstrated significant differential expression in the niCD group. In contrast, nearly 100 miRNAs significantly varied between the iCD and niCD groups. Finally, luciferase reporter gene assays showed that hsa-miR-16-1 directly regulated the human C10orf54 gene and that they were negatively correlated. Conclusions Our results indicated that the differentially expressed miRNAs and mRNAs were related to immune inflammation and intestinal flora. The data provide preliminary evidence that the occurrence of CD involves the inhibition of C10orf54 expression by hsa-miR-16-1.