Most used microRNA in inflammatory bowel disease

MicroRNAs (miRNAs) have recently emerged as important mediators of immune development and responses. miRNAs are short (21–25 nucleotide), non-coding RNA molecules that are most commonly transcribed by RNA polymerase II and processed by proteins such as Drosha and Dicer. MicroRNAs play important roles within the complex intestinal immune system. They can be expressed within hematopoietic cells in response to inflammatory signals from pattern recognition receptors (PRR) and antigen receptors (AR). In this way, miRNAs can regulate immune responses, including secretion of cytokines, chemokines, and antibodies, all of which affect intestinal homeostasis. Within intestinal epithelial cells (IECs) and other non-hematopoietic intestinal cells, miRNAs are expressed in and regulate pathways involved in secretion of antimicrobial peptides, cell renewal, and barrier permeability, among others. These noncoding RNAs function as rheostats to the immune response as opposed to binary switches as they act to adjust the magnitude of gene expression. miRNAs also work in feedback loops, ensuring that the immune system does not produce inappropriately strong responses while also promoting protective immunity when needed. In this way, miRNAs themselves can be considered mediators of homeostasis within the immune system as they act to buffer inflammation. IBD is a chronic relapsing disorder of the gastrointestinal tract that is due to intestinal inflammation and epithelial injury and includes Crohn’s disease and ulcerative colitis. Although IBD is thought to arise through interactions among genetic, immunologic, and environmental factors, the etiology underlying the pathophysiology of IBD remains largely unknown.Studies to date have identified unique miRNA expression profile signatures in IBD and preliminary functional analyses associate these deregulated miRNAs to canonical pathways associated with IBD pathogenesis. UC-associated peripheral blood miRNAs were found to be differentially expressed (increased: miRs-28-5p, -151-5p, -103-2, -199a-5p, -340,-362-3p, -532-3p; decreased: miR-505) miRs-199a-5p, -362-3p, -532-3p, -16, -106a, -195, -340 and miRplusE1271 were increased and miR-149 was decreased in the peripheral blood of patients with CD.In this review, we summarize and discuss the miRNA expression signatures associated with IBD in peripheral blood, highlight miRNAs with potential future clinical applications as diagnostic and therapeutic targets, and provide an outlook on how to develop miRNA based therapies.

Keywords:

inflammatory bowel disease , microRNA , Crohn disease , ulcerative colitis