Role of MicroRNA in Inflammatory Bowel Disease: Clinical Evidence and the Development of Preclinical Animal Models

Abstract

The dysregulation of microRNA (miRNA) is implicated in cancer, inflammation, cardiovascular disorders, drug resistance, and aging. While most researchers study miRNA’s role as a biomarker, for example, to distinguish between various sub-forms or stages of a given disease of interest, research is also ongoing to utilize these small nucleic acids as therapeutics. An example of a common pleiotropic disease that could benefit from miRNA-based therapeutics is inflammatory bowel disease (IBD), which is characterized by chronic inflammation of the small and large intestines. Due to complex interactions between multiple factors in the etiology of IBD, development of therapies that effectively maintain remission for this disease is a significant challenge. In this review, we discuss the role of dysregulated miRNA expression in the context of clinical ulcerative colitis (UC) and Crohn’s disease (CD)—the two main forms of IBD—and the various preclinical mouse models of IBD utilized to validate the therapeutic potential of targeting these miRNA. Additionally, we highlight advances in the development of genetically engineered animal models that recapitulate clinical miRNA expression and provide powerful preclinical models to assess the diagnostic and therapeutic promise of miRNA in IBD.

MicroRNAs in Inflammatory Bowel Disease and Its Complications

“…miRNA antagonists are composed of antisense oligonucleotides that preferentially inhibit miRNA’s “seed regions” to induce silencing of downstream pathways with antagomirs including functional groups for nuclease degradation [ 96 , 97 ]. Suri et al also reported that a variety of interventions that inhibited miR-29a, miR-26b, miR-233, miR-19a, miR-146-5p, and miR-122a were able to restore epithelial barrier integrity and alleviate symptoms of IBD [ 97 ].…”

“…miRNA antagonists are composed of antisense oligonucleotides that preferentially inhibit miRNA’s “seed regions” to induce silencing of downstream pathways with antagomirs including functional groups for nuclease degradation [ 96 , 97 ]. Suri et al also reported that a variety of interventions that inhibited miR-29a, miR-26b, miR-233, miR-19a, miR-146-5p, and miR-122a were able to restore epithelial barrier integrity and alleviate symptoms of IBD [ 97 ]. miR-214 may serve as a potential therapeutic target, as it is overexpressed in UC and CAC colonic tissue and it decreases PTEN and PDLIM2 to activate the NF-κB and AKT signaling pathways and amplify the inflammatory response [ 98 ].…”

miRNAs Can Affect Intestinal Epithelial Barrier in Inflammatory Bowel Disease

“…Suri et al. (2021) had summarized five main approaches of miRNA delivery: lipid carriers (e.g., liposomes and lipid nanoparticles) and polymeric carriers (e.g., cationic carriers such as polyethyleneimine) along with viral vectors, conjugates, and exosomes ( 86 ). Ye et al.…”

The Impact of MicroRNAs during Inflammatory Bowel Disease: Effects on the Mucus Layer and Intercellular Junctions for Gut Permeability

“…The coordinated interplay between immunity regulation and IECs is essential in controlling barrier permeability. Further information on relevant research models used in the study of IBD and their conclusions regarding miRNAs’ impact on pathogenesis has been summarised elsewhere [ 94 ].…”