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

BACKGROUND

Hirschsprung's disease (HSCR) is caused by defective enteric neural crest cell (ENCC) migration. Exosome-transmitted microRNAs are implicated in HSCR pathogenesis, but mechanisms remain unclear.

METHODS

Plasma exosomes and colon tissues were collected from HSCR patients and controls. We assessed the effects of exosomal miR-323a-3p on the proliferation and migration of immortalized ENCC-derived neural cell line (iENC) in vitro using CCK-8, EdU and Transwell assays, and its impact on ENCC migration in vivo using a zebrafish model.

RESULTS

Exosomal miR-323a-3p was significantly upregulated in the plasma of HSCR and exhibited prospective diagnostic relevance (AUC = 0.7269, p = 0.0043). Exosomal miR-323a-3p was taken up by iENCs and suppressed their proliferation and migration. TET2 was identified as a potential miR-323a-3p target. TET2 was downregulated in HSCR aganglionic tissues, and its knockdown inhibited iENC proliferation and migration. In the zebrafish model, exosomal miR-323a-3p impaired distal ENCC colonization.

CONCLUSION

Exosomal miR-323a-3p is upregulated in HSCR and associated with impaired ENCC-derived cell function, potentially via TET2. These findings suggest exosome-transmitted microRNA-323a-3p participated in the occurrence of Hirschsprung's disease and exhibit promising potential as a prospective diagnostic biomarker.