MicroRNAs as multifaceted regulators and therapeutic targets in ulcerative colitis

Area of Science:

• Gastroenterology
• Molecular Biology
• Immunology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by gut barrier defects, immune system dysregulation, and altered gut microbiota.
• MicroRNAs (miRNAs), small non-coding RNA molecules, play crucial roles in regulating gene expression and are implicated in UC pathogenesis.

Purpose of the Study:

• To review the multifaceted roles of miRNAs in UC pathogenesis, covering their impact on the gut barrier, immune system, and microbiota.
• To explore the clinical potential of miRNAs as non-invasive biomarkers for UC diagnosis and monitoring.
• To discuss the therapeutic applications of miRNAs in UC treatment.

Main Methods:

• Literature review of recent mechanistic insights and translational advances in miRNA research related to UC.
• Analysis of miRNA involvement in epithelial cell apoptosis, tight junction integrity, and mucin secretion.
• Examination of miRNA influence on immune cell differentiation and polarization (e.g., Th17/Treg balance).

Main Results:

• Specific miRNAs (e.g., miR-223, miR-151-5p, miR-429) contribute to UC-related barrier dysfunction.
• miRNAs modulate innate and adaptive immune responses, influencing macrophage polarization and T cell differentiation.
• Circulating miRNAs show potential as non-invasive biomarkers for UC diagnosis, activity assessment, and predicting treatment response.
• miRNA-based therapeutics (mimics and inhibitors) demonstrate efficacy in early clinical trials.

Conclusions:

• miRNAs are key regulators in UC, influencing barrier integrity, immune responses, and host-microbe interactions.
• Circulating miRNAs offer a promising avenue for non-invasive diagnostics and monitoring of UC.
• miRNA-targeted therapies represent a novel and potentially effective treatment strategy for UC, complementing existing biologics.