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Review
. 2024 Feb 28;9(3):704-714.
doi: 10.1016/j.ncrna.2024.02.015. eCollection 2024 Sep.

The roles of non-coding RNAs in Hirschsprung's disease

Yang Yang  1 , Xinwei Hou  1 , Chen Wang  1 , Qinming Chen  1 , Yi Lu  1 , Daiyue Yu  1 , Kai Wu  1
Affiliations
Review

The roles of non-coding RNAs in Hirschsprung's disease

Yang Yang et al. Noncoding RNA Res. .

Abstract

Hirschsprung's disease (HSCR) is a congenital disorder characterized by the absence of ganglion cells in the colon, leading to various intestinal complications. The etiology of HSCR stems from complex genetic and environmental interactions, of which the intricate roles of non-coding RNAs (ncRNAs) are a key area of research. However, the roles of ncRNAs in the pathogenesis of HSCR have not been fully elucidated. In order to understand the variety of symptoms caused by HSCR and develop new therapeutic approaches, it is essential to understand the underlying biological genetic basis of HSCR. This review presents a comprehensive overview of the current understanding regarding the involvement of ncRNAs in HSCR, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Additionally, it provides a summary of the molecular mechanisms through which ncRNAs regulate the expression of genes related to the proliferation, migration, and differentiation of intestinal neural crest cells, thereby contributing to the advancement of HSCR research.

Keywords: CircRNAs; Hirschsprung's disease; LncRNAs; MiRNAs; NcRNAs.

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Figures

Fig. 1
Fig. 1
Various intracellular signaling molecules and pathways involved in HSCR. Including receptors like RET, ENDRB; signaling proteins such as AKT, ERK; and transcription factors like SOX10, PHOX2B. Neurotrophic factors such as GDNF, ARTN, PSPN, and NTF3 interact with corresponding receptors GFRα1-4 and NTRK. Additionally, pathways like the NOTCH signaling pathway, Sonic Hedgehog (SHH) pathway, as well as other molecules (such as SEMA3C and SEMA3D), play significant roles in enteric neurons.
Fig. 2
Fig. 2
The formation process and related biological functions of ncRNAs. DNA transcription results in primary microRNA (pri-miRNA), long non-coding RNA (lncRNA), and precursor messenger RNA (pre-mRNA). Pri-miRNA is cleaved by Drosha enzyme to form precursor miRNA (pre-miRNA), which is transported by Exportin-5. Dicer enzyme processes pre-miRNA into mature miRNA, promoting the loading of RNA-induced silencing complex (RISC) for targeted mRNA silencing. In the nucleus, lncRNA binds to gene promoter regions, promoting transcription. In the cytoplasm, lncRNA can bind with miRNA and mRNA to exert its function. Eventually degraded into monoribonucleotides. Pre-mRNA undergoes splicing, resulting in coding regions (exons) shown in purple to form circRNA. It regulates downstream gene expression by binding with miRNA or Ribonucleoprotein particles (RBPs).
Fig. 3
Fig. 3
NcRNAs related to cell apoptosis, proliferation, migration, and differentiation in HSCR. Green represents ncRNAs involved in influencing cell apoptosis, blue indicates ncRNAs involved in cell migration and proliferation, and red symbolizes ncRNAs involved in cell differentiation. Moreover, arrows and symbols are used to the regulatory direction of various ncRNAs on their target genes or pathways (where “+” signifies promotion and “-” indicates inhibition).
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