MicroRNAs overexpressed in Crohn’s disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn’s disease pathogenesis

Abstract

Background In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. Methods We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. Results We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. Conclusion The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.

Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review

“…Environmental factors such as pathogenic microorganisms, microbiota, diet, smoking, and psychosocial factors also play an important role in its pathogenesis. Thus, improving life habits could change the microbiome to eubiosis, contributing to the stabilization of the disease [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ].…”

“…Innate and adaptive immunities are the primary controllers of CD pathogenesis. The inflammatory process seems to be caused mainly by the failure of innate recognition of several bacteria, by the impaired intestinal barrier integrity, and by the spread of luminal pathogens through the intestinal wall, as previously mentioned, overloading innate immune cells to recognize and eliminate invaders [ 81 , 84 , 89 ].…”

Nutritional Treatment in Crohn’s Disease

“…Epigenetic alterations play a primary role in CD orchestration. A recent study shed light on the cross-talk between the miRNA and epigenetic mechanisms implicated in CD development, finding 26 miRNAs highly expressed in CD patients and modulating epigenetic modifications putatively involved with CD progression [ 139 ]. In particular, miR-21, which controls the innate and adaptative immune system and hypomethylation of the miR-21 locus, was found to correlate with increased primary miR-21 expression in leucocytes and in inflamed intestinal mucosa [ 140 ].…”

The Role of Glycosyltransferases in Colorectal Cancer

“…Since mucins are one of the most important components of the gastrointestinal associated immune system, alterations in mucin expression or in their structure and functional properties due to changes in N-glycosylation and O-glycosylation patterns among other PTMs have shown a role in immune dysregulation, loss of mucosal barrier integrity, increased risk of inflammatory or infectious diseases and changes in cell adhesive properties that alter the interaction between cells and their microenvironment [ 82 ]. In this regard, the CRC risk increases in patients affected by inflammatory bowel diseases (IBD), which are characterized by a marked dysbiosis, anomalous immunological response against gut microbiota, epigenetic dysregulation and alterations in the expression of enzymes associated with PTMs [ 83 ]. Thus, mucins’ contribution to IBD and CRC pathogenesis has been studied by several research efforts.…”

“…Interestingly, mucin oligosaccharides are a source of nourishment for microbiota and participates in the maintenance of colonic flora balance and distribution. Therefore, alterations in mucin glycans can generate dysbiosis and consequently abrogate gut immune balance and intestinal mucosal integrity [ 83 ]. In addition, a dense and diverse O-glycosylation pattern of mucins, such as MUC2 described as the main gel-forming mucin, is a key protective factor against colitis and CRC through the supply of health nourishment for the gut microbiota, maintenance of mucus bacterial adhesion capacity and protection from digestive proteases [ 19 , 86 ].…”