Intestinal and Circulating MicroRNAs in Coeliac Disease

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play a key role in the pathogenesis of autoimmune and gastrointestinal diseases. Previous studies have revealed that miRNAs are dysregulated in intestinal biopsies of patients affected by coeliac disease (CD). Combined bioinformatics analyses of miRNA expression profiles and mRNA target genes as classified by Gene Ontology, are powerful tools to investigate the functional role of miRNAs in coeliac disease. However, little is still known about the function of circulating miRNAs, their expression level compared to tissue miRNAs, and whether the mechanisms of post-transcriptional regulation are the same of tissue miRNAs. In any case, if we assume that a cell-cell communication process has to occur, and that circulating miRNAs are delivered to recipient cells, we can derive useful information by performing target predictions. Interestingly, all of the mRNA targets of dysregulated miRNAs reported in the literature (i.e., miR-31-5p, miR-192, miR-194, miR-449a and miR-638) belong to several important biological processes, such as Wnt signaling, cell proliferation and differentiation, and adherens junction pathways. Although we think that these predictions have to be necessarily confirmed by "wet-lab" data, the miRNAs dysregulated during the development of CD could be potentially involved in the pathogenesis of coeliac disease and their correlation with circulating miRNAs offers new possibilities to use them as disease biomarkers.

Keywords: biomarkers; circulating microRNAs; coeliac disease; tissue microRNAs.

Figure 1

The small intestinal mucosa of a healthy individual (left) compared to that of coeliac patients (right). The gluten exposure induces a damage of the intestinal mucosa characterized by a complete loss of villi and crypts hyperplasia.

Figure 2

Schematic representation of miRNAs found deregulated in human small intestine of patients with CD and their target genes and reported in the literature (colored boxes). Upregulated (red) or downregulated miRNAs (green) can target many genes (indicated by blue arrows). Bioinformatics predictions on these genes allowed to obtain additional pathways (grey boxes) directly implicated in CD, as discussed in this review. Although not comprehensively, these genes extend the picture of the biological processes involved in CD.