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Updated: Mar 29, 2026
Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative
Georgios Koukos1, Christos Polytarchou, Jess L Kaplan
1Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California; Institute for Molecular Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts.
Insights
MicroRNA-124 (miR-124) levels are reduced in children with active ulcerative colitis (UC), leading to increased STAT3 activity. This suggests miR-124 plays a role in pediatric UC pathogenesis.
Area of Science:
- Molecular Biology
- Gastroenterology
- Immunology
Background:
- MicroRNAs (miRs) are implicated in inflammatory bowel diseases (IBDs), but their specific roles in pediatric IBD remain unclear.
- Investigating colonic mucosal miRs in children with ulcerative colitis (UC) is crucial for understanding disease mechanisms.
Purpose of the Study:
- To determine if colonic mucosal microRNAs (miRs) are altered in children diagnosed with ulcerative colitis (UC).
- To explore the regulatory relationship between miR-124 and signal transducer and activator of transcription 3 (STAT3) in pediatric UC.
Main Methods:
- Utilized a library of 316 miRs to identify those regulating STAT3 phosphorylation in human colonocytes.
- Quantified miR-124 levels in colon biopsies from pediatric UC patients and controls using real-time polymerase chain reaction.
- Assessed MIR124 promoter methylation and STAT3 messenger RNA (mRNA) levels in relation to miR-124 expression.
Main Results:
- Phosphorylated STAT3 and its downstream targets were elevated in pediatric UC patients.
- miR-124 was significantly down-regulated in colon tissues of children with active UC and directly targeted STAT3 mRNA.
- Down-regulation of miR-124 in pediatric UC was linked to hypermethylation of its promoter region.
Conclusions:
- miR-124 negatively regulates STAT3 expression, a key factor in inflammation.
- Reduced miR-124 levels in children with active UC may contribute to increased STAT3 activity, promoting UC pathogenesis.
- miR-124 represents a potential therapeutic target for pediatric ulcerative colitis.
Background & Aims:
Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC).
Methods:
We used a library of 316 miRs to identify those that regulate phosphorylation of signal transducer and activator of transcription 3 (STAT3) in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time polymerase chain reaction analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2'-deoxycytidine (5-AZA). Methylation of the MIR124 promoter was measured by quantitative methylation-specific polymerase chain reaction.
Results:
Levels of phosphorylated STAT3 and the genes it regulates (encoding vascular endothelial growth factor (VEGF), BCL2, BCLXL, and matrix metallopeptidase 9 [MMP9]) were increased in pediatric patients with UC compared with control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by ≥ 75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was down-regulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 messenger RNA (mRNA). Levels of miR-124 were decreased, whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC compared with those with inactive disease. In addition, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Down-regulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-AZA up-regulated miR-124 and reduced levels of STAT3 mRNA.
Conclusions:
miR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and the pathogenesis of UC in children.
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