Abstract
Research on inflammatory bowel disease (IBD) has produced mounting evidence for the modulation of microRNAs (miRNAs) during pathogenesis. MiRNAs are small, non-coding RNAs that interfere with the translation of mRNAs. Their high stability in free circulation at various regions of the body allows researchers to utilise miRNAs as biomarkers and as a focus for potential treatments of IBD. Yet, their distinct regulatory roles at the gut epithelial barrier remain elusive due to the fact that there are several external and cellular factors contributing to gut permeability. This review focuses on how miRNAs may compromise two components of the gut epithelium that together form the initial physical barrier: the mucus layer and the intercellular epithelial junctions. Here, we summarise the impact of miRNAs on goblet cell secretion and mucin structure, along with the proper function of various junctional proteins involved in paracellular transport, cell adhesion and communication. Knowledge of how this elaborate network of cells at the gut epithelial barrier becomes compromised as a result of dysregulated miRNA expression, thereby contributing to the development of IBD, will support the generation of miRNA-associated biomarker panels and therapeutic strategies that detect and ameliorate gut permeability.
Highlights
Published: 30 November 2021Since their discovery in 1993 [1,2], microRNAs were shown to play critical roles in various biological processes
RNA-induced silencing complex (RISC)-targeted RNA molecules are recognised by sequence-specific binding and Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Another study demonstrated that miR-20b, miR-26b, miR-98, miR-99a and miR-203 were significantly upregulated in colonic mucosal pinch biopsies obtained from patients with active ulcerative colitis (UC) compared to quiescent UC [47]
Summary
Since their discovery in 1993 [1,2], microRNAs (miRNAs) were shown to play critical roles in various biological processes. MiRNAs are encoded within intergenic, intronic and exonic regions of the human genome [7], with the majority of miRNAs found in the intronic regions of both protein-coding and non-coding genes [8]. Their biogenesis starts with a primary (pri)-miRNA molecule of nuclear, hairpin-structure. The guidance strand of the miRNA duplex is loaded into an Argonaute (AGO) protein, forming the RNA-induced silencing complex (RISC) [3,4]. Whether the binding of an miRNA to its target mRNA leads to the inhibition of the translational process or to mRNA degradation is determined by the specific binding capacity. We have summarised the key research on the immunological roles of miRNAs relevant to IBD, their potential uses as diagnostic biomarkers and treatments, and focus on their role in gut permeability
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