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.

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