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Exosome-transmitted microRNA-323a-3p participated in the occurrence of Hirschsprung's disease

Haoran Shen1,2, Chenglong Wang1, Xiurui Lv3

  • 1Department of Neonatal Surgery, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Epigenomics
|March 30, 2026
PubMed
Abstract

Insights

Exosomes carrying microRNA-323a-3p are elevated in Hirschsprung

Area of Science:

  • Gastroenterology
  • Developmental Biology
  • Molecular Biology

Background:

  • Hirschsprung's disease (HSCR) results from impaired enteric neural crest cell (ENCC) migration.
  • The role of exosome-mediated microRNAs in HSCR pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the function of exosomal microRNA-323a-3p in HSCR.
  • To assess its potential as a diagnostic biomarker for HSCR.

Main Methods:

  • Collected plasma exosomes and colon tissues from HSCR patients and controls.
  • Assessed exosomal miR-323a-3p effects on immortalized ENCC-derived neural cells (iENCs) in vitro and ENCC migration in vivo using a zebrafish model.

Main Results:

  • Exosomal miR-323a-3p was significantly upregulated in HSCR patients and showed diagnostic potential (AUC=0.7269).
  • Exosomal miR-323a-3p suppressed iENC proliferation and migration, potentially by targeting TET2.
  • TET2 downregulation inhibited iENC function, and exosomal miR-323a-3p impaired ENCC colonization in zebrafish.

Conclusions:

  • Exosomal miR-323a-3p is upregulated in HSCR and impairs ENCC function, possibly via TET2.
  • Exosomal miR-323a-3p shows potential as a diagnostic biomarker for Hirschsprung's disease.
Keywords:
Hirschsprung’s diseaseenteric nervous systemexosomesmicroRNAsneural crest cells

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