Bioinformatics Analysis of Differentially Expressed miRNAs and Their Related Genes From Plasma-Derived Exosomes in TCA

Background: Hirschsprung’s disease (HSCR), a congenital disorder characterized by spasticity and narrowing of the distal colon, as well as abnormalities in peristalsis and defecation, is caused by a deficit of the enteric nervous system of the distal gut. Total colonic aganglionosis (TCA) is a rare type of HSCR. This study aimed to find key microRNAs (miRNAs) and their associated genes from plasma-derived exosomes, as potential biomarkers to study TCA pathogenesis. Results: : Plasma-derived exosomal miRNA sequencing of samples from 9 children with HSCR and 10 matched children without HSCR revealed that 62 miRNAs were differentially expressed in plasma-derived exosomes, of which 31 were up-regulated and 31 were down-regulated. The target genes of DEM are predicted from three common databases.There were 652 DEM target gene pairs for the 31 DEMs that were up-regulated and 234 pairs for the 31 DEMs that were down-regulated. Furthermore, 4 DEMs: miR-106b-5p, miR-205-5p, miR-375-3p and miR-34a-5p were differentially expressed between other HSCR types and TCA. Conclusions: : Four key miRNAs (miR-106b-5p, miR-205-5p, miR-375-3p, and miR-34a-5p) and their interacting four key genes AF4/FMR2 family member 4 (AFF4), myotubularin-related protein 9 gene (MTMR9), POU domain class 2 transcription factor 1 (POU2F1), and WW-and-C2-domain-containing(WWC2) may be involved in the pathogenesis of TCA.