Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease

Abstract

Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor β cell–cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.

Crosstalk between MicroRNAs and Oxidative Stress in Coeliac Disease

“…Our pilot study did not find any statistically significant differences in the levels of miRNAs and oxidative stress markers between the different groups evaluated, as well as no correlations between different miRNAs and 8-OHdG in all groups (except for a positive correlation with miR-200 and a negative correlation with miR-1226 in CeD-GFD as a trend toward significance). Interestingly, we found particularly high levels of miR-1226 in patients with complicated CeD, similarly to what has been found in other studies [ 38 ], but no conclusions can be drawn from our findings due to the very limited number of patients evaluated. In order to demonstrated the role of miRNAs and oxidative stress in the pathogenesis of CeD and that these two influence each other.…”

“…In contrast, others could be potentially useful in predicting the progression toward intestinal T-cell lymphoma related to oncogenesis (through activation of STAT3 and c-Myc). A recent study identified several upregulated miRNAs characterizing RCD type 2 that could be monitored in patient serum: miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p [ 38 ]. These miRNAs were involved in pathways of response to TGF-β, cell-cell response to Wnt, epigenetic regulation, and inflammatory profiles.…”