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.
Highlights
Inflammatory bowel disease (IBD) is a multifactorial progressive disease marked by recurrent chronic inflammation of the gastrointestinal tract, a dysregulated immune system, and dysbiosis [1,2,3,4]
Regulatory ncRNAs are sub-classified on the basis of size into small ncRNAs, which are usually less than 200 nucleotides in length, and long ncRNA greater than 200 nts [19]. sncRNAs include microRNA, small interfering RNA, and piwi-interacting RNA [17]
While this study clearly demonstrates the significance of miRNAs in the pathogenesis of IBD, and that miRNAs are potential therapeutic targets in IBD, this indicates the care required in model selection, with ideally more than one mouse model being used for preclinical validation of therapeutic targets
Summary
Inflammatory bowel disease (IBD) is a multifactorial progressive disease marked by recurrent chronic inflammation of the gastrointestinal tract, a dysregulated immune system, and dysbiosis [1,2,3,4]. Chronic diarrhea, weight loss, exhaustion, and anorexia are common symptoms among younger CD patients. Preferred therapeutic agents for CD include immunosuppressants (e.g., azathioprine, mercaptopurine, and methotrexate), corticosteroids, anti-TNF therapy (e.g., Adalimumab and Infliximab), monoclonal antibodies (e.g., Vedolizumab and Ustekinumab), and surgery for patients who do not respond to treatment [8,9]. In UC, only the colonic mucosa is inflamed, and the major symptoms include rectal tenesmus, bleeding, diarrhea, abdominal pain, and fecal incontinence. 5-Aminosalicylic acid (oral, suppository, or enema), corticosteroids, anti-TNF agents (e.g., Infliximab, Golimumab, Adalimumab), and monoclonal antibodies (e.g., Vedolizumab and Ustekinumab) [8,10]. We review clinically relevant miRNAs that have been validated in various mouse models of IBD
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