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Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Expression Alterations and Correlative Analysis of TPH1/hsa-miR-194-5p/NEAT1 and MAOA/hsa-miR-1276/NEAT1 Axes in
Mehmet Tughan Kiziltug1, Mehmet Emin Erdal2, Bahar Tasdelen3
1Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, 80337 Munich, Germany.
Insights
Pediatric inflammatory bowel disease (pIBD) involves altered serotonin metabolism and non-coding RNAs (ncRNAs). Tryptophan hydroxylase 1 (TPH1) and Nuclear Enriched Abundant Transcript 1 (NEAT1) show strong associations, suggesting a role in pIBD.
Area of Science:
- Gastroenterology and Molecular Biology
- Pediatric Inflammatory Bowel Disease (pIBD) research
- Serotonin metabolism and non-coding RNA (ncRNA) interactions
Background:
- Pediatric inflammatory bowel disease (pIBD), including ulcerative colitis (UC) and Crohn's disease (CD), has complex underlying mechanisms.
- Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are implicated in disease pathogenesis.
- Serotonin metabolism enzymes, specifically Tryptophan hydroxylase 1 (TPH1) and Monoamine oxidase A (MAOA), are critical for intestinal function and inflammation.
Purpose of the Study:
- To investigate the expression patterns of TPH1, MAOA, hsa-miR-194-5p, hsa-miR-1276, and the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in pediatric IBD.
- To explore the relationship between these molecules and intestinal inflammation in pIBD patients.
- To identify potential molecular pathways, such as the TPH1/miR-194-5p/NEAT1 axis, involved in pIBD pathophysiology.
Main Methods:
- Analysis of gene and ncRNA expression in intestinal tissue biopsies and peripheral blood from pIBD patients and healthy controls.
- Quantitative assessment of TPH1, MAOA, hsa-miR-194-5p, hsa-miR-1276, and NEAT1.
- Statistical analysis including subgroup analysis for UC patients and correlation analysis between key molecules.
Main Results:
- TPH1 expression was significantly elevated in the inflamed transverse colon.
- MAOA expression was reduced in multiple intestinal regions, including the ileum and descending colon, with further decreases in inflamed areas.
- hsa-miR-194-5p was upregulated in several colonic regions and in the blood of UC patients. NEAT1 showed region-specific changes, increasing in the ascending colon and decreasing in the ileum. Strong positive correlations were observed between TPH1 and NEAT1 in the ileum and transverse colon.
Conclusions:
- The study reveals region-specific dysregulation of serotonin-related genes and ncRNAs in pediatric IBD.
- The identified TPH1/miR-194-5p/NEAT1 axis represents a potential contributor to pIBD pathophysiology.
- Further mechanistic studies are warranted to elucidate the precise role of these molecules in disease development and progression.
Abstract:
Pediatric inflammatory bowel disease (pIBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), involves complex mechanisms that include non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), alongside enzymes regulating serotonin metabolism. Tryptophan hydroxylase 1 (TPH1) and monoamine oxidase A (MAOA) play critical roles in serotonin turnover and may contribute to intestinal inflammation. We investigated the expression of TPH1, MAOA, hsa-miR-194-5p, hsa-miR-1276, and the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in intestinal tissue biopsies and peripheral blood from pIBD patients and controls. TPH1 was significantly elevated in the inflamed transverse colon (p = 0.034), whereas MAOA was reduced in the ileum (p = 0.041) and descending colon (p = 0.001), with further decreases in inflamed ileum (p < 0.001), ascending (p = 0.008), and descending colon (p = 0.001). Subgroup analysis revealed decreased MAOA in the ascending colon of UC patients (p = 0.011). hsa-miR-194-5p was upregulated in the transverse colon (p = 0.015), inflamed transverse (p = 0.013) and descending colon (p = 0.015), and in blood of UC patients (p = 0.01). NEAT1 expression increased in the ascending colon (p = 0.042) but decreased in the ileum (p = 0.006). Correlation analysis showed strong positive associations between TPH1 and NEAT1 in the ileum (r = 0.945, p < 0.01) and transverse colon (r = 0.609, p < 0.01). These results highlight region-specific dysregulation of serotonin-related genes and ncRNAs in pIBD, with the TPH1/miR-194-5p/NEAT1 axis potentially contributing to disease pathophysiology and warranting further mechanistic investigation.
