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Updated: Nov 16, 2025
Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
The Colonic Mucosal MicroRNAs, MicroRNA-219a-5p, and MicroRNA-338-3p Are Downregulated in Irritable Bowel Syndrome
Swapna Mahurkar-Joshi1, Carl Robert Rankin2, Elizabeth Jane Videlock1
1G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Background & Aims:
Alterations in microRNA (miRNA) and in the intestinal barrier are putative risk factors for irritable bowel syndrome (IBS). We aimed to identify differentially expressed colonic mucosal miRNAs, their targets in IBS compared to healthy controls (HCs), and putative downstream pathways.
Methods:
Twenty-nine IBS patients (15 IBS with constipation [IBS-C], 14 IBS with diarrhea [IBS-D]), and 15 age-matched HCs underwent sigmoidoscopy with biopsies. A nCounter array was used to assess biopsy specimen-associated miRNA levels. A false discovery rate (FDR) < 10% was considered significant. Real-time polymerase chain reaction (PCR) was used to validate differentially expressed genes. To assess barrier function, trans-epithelial electrical resistance (TEER) and dextran flux assays were performed on Caco-2 intestinal epithelial cells that were transfected with miRNA-inhibitors or control inhibitors. Protein expression of barrier function associated genes was confirmed using western blots.
Results:
Four out of 247 miRNAs tested were differentially expressed in IBS compared to HCs (FDR < 10%). Real-time PCR validation suggested decreased levels of miR-219a-5p and miR-338-3p in IBS (P = .026 and P = .004), and IBS-C (P = .02 and P = .06) vs. HCs as the strongest associations. Inhibition of miR-219a-5p resulted in altered expression of proteasome/barrier function genes. Functionally, miR-219a-5p inhibition enhanced the permeability of intestinal epithelial cells as TEER was reduced (25-50%, P < .05) and dextran flux was increased (P < .01). Additionally, inhibition of miR-338-3p in cells caused alterations in the mitogen-activated protein kinase (MAPK) signaling pathway genes.
Conclusion:
Two microRNAs that potentially affect permeability and visceral nociception were identified to be altered in IBS patients. MiR-219a-5p and miR-338-3p potentially alter barrier function and visceral hypersensitivity via neuronal and MAPK signaling and could be therapeutic targets in IBS.
Insights
Altered microRNAs (miRNAs) in the colon are linked to irritable bowel syndrome (IBS). Decreased miR-219a-5p and miR-338-3p impact intestinal barrier function and may be therapeutic targets for IBS.
Area of Science:
- Gastroenterology
- Molecular Biology
- MicroRNA Research
Background:
- Irritable bowel syndrome (IBS) is associated with microRNA (miRNA) alterations and intestinal barrier dysfunction.
- Identifying specific miRNAs and their roles is crucial for understanding IBS pathogenesis.
Purpose of the Study:
- To identify differentially expressed colonic mucosal miRNAs in IBS patients compared to healthy controls (HCs).
- To investigate the functional impact of these miRNAs on intestinal barrier function and downstream pathways.
- To explore potential therapeutic targets for IBS.
Main Methods:
- Colonic biopsies from 29 IBS patients (IBS-C and IBS-D) and 15 HCs were analyzed for miRNA expression using nCounter arrays.
- Differentially expressed miRNAs were validated by real-time PCR.
- In vitro assays (TEER, dextran flux, western blot) were performed on Caco-2 cells transfected with miRNA inhibitors to assess barrier function.
- MAPK signaling pathway gene expression was also analyzed.
Main Results:
- Four out of 247 miRNAs were significantly altered in IBS patients (FDR < 10%).
- Decreased levels of miR-219a-5p and miR-338-3p were strongly associated with IBS and IBS with constipation (IBS-C).
- Inhibition of miR-219a-5p impaired intestinal epithelial barrier function, increasing permeability.
- Inhibition of miR-338-3p affected MAPK signaling pathway genes.
Conclusions:
- Two miRNAs, miR-219a-5p and miR-338-3p, are altered in IBS patients.
- These miRNAs may influence intestinal permeability and visceral nociception.
- MiR-219a-5p and miR-338-3p represent potential therapeutic targets for IBS by modulating barrier function and signaling pathways.
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