miRNAs as Biomarkers and Therapeutic Targets in Celiac Disease: Current Advances and Future Directions

Abstract

This in-depth review examines the complex interactions between miRNAs and Celiac disease (CD) across various biological aspects. The discussion begins with an in-depth examination of miRNAs' biogenesis and functional pathways, highlighting their critical regulatory roles in cellular processes. The exploration extends to CD pathogenesis, elucidating how miRNAs contribute to the aberrant immune response against gluten in the small intestine. We navigate miRNAs' regulatory influence on intestinal development and innate and adaptive immunity, providing a panoramic view of their impact on CD etiology. Some miRNAs, such as miR-449a, miR-192-5p, miR-31-5p, miR-17, miR-30a, miR-638, miR-192, miR-194-5p, and miR-197, are dysregulated in CD and are involved in various pathways, including Notch1, tight junctions, and other pathogenetic pathways. The clinical importance of miRNAs takes center stage, unveiling their potential as diagnostic and prognostic markers and reshaping CD management. Investigating miRNA-based therapeutic interventions opens avenues for precision medicine in modulating CD's immune dysregulation. With clinical advancements such as locked nucleic acid-modified antimiRs that target miR-122 for the treatment of hepatitis C and miR-34a mimics for hepatocellular carcinoma, microRNAs are promising therapeutic targets. Additionally, novel delivery systems such as lipid nanoparticles and tissue-specific conjugates address the crucial challenges of targeted miRNA modulation. Extracellular vesicle miRNAs add a layer of complexity, acting as mediators in CD's systemic effects. Finally, we outline future perspectives, envisioning how the evolving landscape of miRNA research can propel advancements in understanding, diagnosis, and treatment, marking this review as a cornerstone for researchers and clinicians in the dynamic field of miRNAs and CD.