MicroRNA Modulation in Inflammatory Bowel Disease

MicroRNAs (miRNAs) are small, non-coding RNAs that fine-tune gene expression post-transcriptionally and have emerged as pivotal regulators of intestinal homeostasis and inflammatory processes. In inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, aberrant miRNA expression contributes to dysregulated immune responses, epithelial barrier dysfunction and heightened risk of complications such as colitis-associated cancer. Key miRNAs act within both immune and structural compartments of the gut to influence cytokine signalling, barrier integrity and epithelial repair. Therapeutic strategies under investigation include miRNA mimics to restore protective functions and antagomirs to inhibit pro-inflammatory species. Advances in delivery systems, from lipid nanoparticles to targeted vesicles, are improving stability and tissue specificity. Emerging high-resolution tools, including single-cell RNA sequencing, are revealing cell-type-specific miRNA profiles and their regulatory networks, enabling precise identification of diagnostic biomarkers and therapeutic targets. Collectively, research over the past two years has deepened understanding of miRNA-mediated cross-talk between the immune system and intestinal epithelium, paving the way for innovative clinical applications in IBD management.

Research from Nature Portfolio

Recent studies have delineated miR-146a as a critical brake on tumour-promoting inflammation in the colon. Within myeloid cells, miR-146a targets key intermediates of the NOD2 pathway to limit IL-17–inducing cytokine release, thereby restraining colonic IL-17 signalling. Concurrently, in intestinal epithelial cells, miR-146a suppresses mediators of IL-17 receptor signalling and prostaglandin synthesis, dampening epithelial responsiveness and limiting tumourigenesis. Preclinical administration of a miR-146a mimic or pharmacological inhibitors of its targets has been shown to alleviate colonic inflammation and suppress progression to colorectal cancer. These findings not only highlight dual-compartment regulation by a single miRNA but also validate miRNA mimic therapy and target inhibition as viable strategies for controlling chronic inflammation and cancer risk in IBD patients.

MicroRNA Modulation in Inflammatory Bowel Disease publication trend

The graph below shows the total number of articles in microrna modulation in inflammatory bowel disease across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA (miRNA): Small non-coding RNA molecules that regulate gene expression by binding to target mRNAs, leading to translational repression or degradation.

Antagomir: Chemically modified oligonucleotide designed to specifically inhibit the function of a target miRNA.

MiRNA mimic: Synthetic double-stranded RNA molecule that restores or enhances the function of a specific miRNA in cells.

Single-cell RNA sequencing: High-resolution technique that profiles gene expression, including miRNAs and mRNAs, at the individual cell level to reveal cellular heterogeneity.

IL-17 signalling: Inflammatory cytokine pathway often upregulated in IBD, mediating recruitment and activation of immune cells within the gut mucosa.

References

1. MicroRNA-146a limits tumorigenic inflammation in colorectal cancer. Nature Communications (2021).
2. The landscape of miRNA-mRNA regulatory network and cellular sources in inflammatory bowel diseases: insights from text mining and single cell RNA sequencing analysis. Frontiers in Immunology (2024).
3. MicroRNA-based therapeutics for inflammatory disorders of the microbiota-gut-brain axis. Pharmacological Research (2023).
4. Non‐coding RNAs and colitis‐associated cancer: Mechanisms and clinical applications. Clinical and Translational Medicine (2023).