Wang Juping,Yan Yingnan,Zhao Fangzheng,et al.Molecular mechanism of hsacirc_049751 influencing the pathogenesis of Hirschsprung’s disease via neural cell migration[J].Journal of Clinical Pediatric Surgery,,():552-557.[doi:10.3760/cma.j.cn101785-20251112-00061]
Molecular mechanism of hsacirc_049751 influencing the pathogenesis of Hirschsprung’s disease via neural cell migration
- Keywords:
- Hirschsprung Disease; Sequence Analysis; RNA; Circular RNA; Glial Cell Line-derived Neurotrophic Factor; Enteric Nervous System
- Abstract:
- Objective To explore the expression profile of circular RNA hsacirc_049751 in Hirschsprung’s disease (HSCR) tissues and preliminarily examine its potential molecular regulatory mechanisms. Methods High-throughput RNA sequencing (Illumina HiSeq) was performed on intestinal tissues from HSCR children and normal controls to identify differentially expressed circRNAs.The expression of hsacirc_049751 was further validated in an expanded cohort by quantitative real-time polymerase chain reaction (qRT-PCR).Bioinformatic analyses were conducted for predicting potential miRNAs interacting with hsacirc_049751 and their downstream target genes.Functional assays were performed in SH-SY5Y cells through an over-expression or a knockdown of hsacirc_049751.And its effects on neural cell migration were evaluated by wound healing assay (WHA). Results Multiple circRNAs became significantly dysregulated in HSCR tissues.qRT-PCR validation demonstrated that hsacirc_049751 was markedly down-regulated in HSCR as compared with normal controls (P<0.01).Functional assays indicated that an over-expression of hsacirc_049751 greatly enhanced SH-SY5Y cell migration,whereas an inhibition of hsacirc_049751 significantly suppressed the migratory capacity of these cells.Bioinformatic predictions revealed that hsacirc_049751 might function as a competing endogenous RNA by sponging miR-516b,thereby attenuating its inhibitory effects on glial cell line-derived neurotrophic factor (GDNF) and glial cell line-derived neurotrophic factor family receptor alpha 3 (GFRA3).Both are key components of enteric nervous system development-related signaling pathways. Conclusions Hsacirc_049751 becomes significantly down-regulated in HSCR and may influence enteric nervous system development through regulating the axis of miR-516b-GDNF/GFRA3 signaling.These findings provide novel mechanistic insights into the molecular pathogenesis of HSCR and hint at potential diagnostic and therapeutic targets.
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Memo
收稿日期:2025-11-12。
基金项目:上海市自然科学基金(22ZR1451500)
通讯作者:王阳,Email:wangyangwy@shsmu.edu.cn