PWE-066 Microrna signatures can differentiate between inflamed and non inflamed colonic mucosa of ulcerative colitis patients

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Abstract

Introduction

Ulcerative colitis (UC) is a form of inflammatory bowel diseases (IBD) which are chronic, relapsing and idiopathic disorders of gastrointestinal tract. The aetiology of IBD has not been defined yet but a complex interplay of microbial, genetic and environmental factors is known to play role in its pathogenesis. Recently, microRNAs have emerged as an epigenetic regulator of inflammation during IBD. MicroRNA target the genes involved in major signalling pathways and regulate there expression thereby affecting the overall inflammatory pathway. In this study we looked at the miRNA profile of inflamed and non inflamed regions of UC patients. We also studied the biological relevance of this dysregulated expression by looking at the potential targets of these miRNA and the biological pathways involved.

Methods

To investigate the expression profile of miRNAs we collected the colonic mucosal biopsies from the endoscopically inflamed and non inflamed regions of UC patients. Colonic biopsies were also collected from control individuals. The differential expression of miRNA was studied by microarray and qRT-PCR. The potential targets of miRNA were predicted using bioinformatics tools such as TargetScan, MIRDB, DIANA-MicroT, microrna.org and Pictar. The pathways involved were identified by mirPath v.3:DIANA TOOLS.

Results

The miRNA profile of inflamed colonic mucosa was found to be significantly different from the non inflamed one in microarray. The real time analysis showed a significant upregulation in the expression of miR-125b and miR-223 in the inflamed colonic mucosa as compared to non inflamed mucosa. TRAF6 which is a potential target of miR-125b and an important signalling molecule of NFkB pathway, showed a significant downregulation in UC patients as compared to controls. Similarly, IKK alpha which is targeted by miR-223 showed a significant downregulation in its expression in UC patients.

Conclusions

Our study indicate towards the spatial expression of miRNA during UC and their biological relevance. MiR-223 showed a disease independent behaviour therefore, it could be developed as a biomarker for UC. Studying these miRNA and the signalling pathways in detail, could provide better insight of disease pathogenesis and provide scope for their use in therapeutics.

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