Evidence map›Paper›PMID 40750918›Full record

ArticlePediatric research2026

circANKRD12/circTIMMDC1 synergistically regulates enteric neural crest cell migration via miR-181b-5p-PROX1-NOTCH1 axis in Hirschsprung's disease.

Runxi Fu, Chen Wang, Ze Xu, Jinyang Zhai, Yuling Zhao, Xiaowei Liu, Ying Zhou, Peilin Gu, Weihua Pan, Yang Wang and 1 more

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Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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11 authors.

Runxi FuDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chen WangDepartment of Pediatric Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ze XuDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jinyang ZhaiDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuling ZhaoDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaowei LiuDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ying ZhouDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peilin GuShanghai Institute for Pediatric Research, Shanghai, China.
Weihua PanDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang WangDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangyangwy@shsmu.edu.cn.
Wei CaiDepartment of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. caiw1978@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCircular RNAs (circRNAs) are implicated in Hirschsprung's disease (HSCR), a genetic disorder caused by defective migration and proliferation of enteric neural crest cells (ENCCs).

methodsExpression patterns of circANKRD12 and circTIMMDC1, and related molecules in the miR-181b-5p-PROX1-NOTCH1 axis were analyzed in human and mouse fetal intestines and HSCR patient tissues. Functional assays, including in vitro neural cell experiments, ex vivo ENCC explant, and in vivo zebrafish models, were conducted to assess the effects on neural cell behavior.

resultscircANKRD12 and circTIMMDC1 were significantly downregulated in HSCR patient tissues. Single-cell analysis confirmed PROX1, NOTCH1, and HES1 expression in ENCCs from human and mouse fetal intestines. Both circRNAs synergistically regulated PROX1 by sponging miR-181b-5p, activating the NOTCH1-HES1 signaling pathway, and enhancing neural cell migration. Knockdown of these circRNAs impaired ENCC proliferation and migration. Zebrafish lacking prox1a showed reduced enteric neurons.

conclusionscircANKRD12 and circTIMMDC1 synergistically modulate ENCC function via the miR-181b-5p-PROX1-NOTCH1 axis, providing insights into HSCR pathogenesis and potential therapies. IMPACT: The study identifies circANKRD12 and circTIMMDC1 as pathogenic circRNAs in HSCR, revealing their synergistic effects on regulating ENCC migration. The study reveals that prox1a (human PROX1 homolog) deficiency in zebrafish induces HSCR-like phenotypes. The study elucidates the detailed mechanistic insights into the circANKRD12/circTIMMDC1-miR-181b-5p-PROX1-NOTCH1 axis in ENCC migration. The study contributes to the development of diagnostic tools and therapies targeting the ceRNA network in HSCR, alongside improved prenatal screening methods for early detection.

Indexed as

Cell MovementEnteric Nervous SystemHirschsprung DiseaseHomeodomain ProteinsMicroRNAsNeural CrestReceptor, Notch1RNA, CircularTumor Suppressor ProteinsAnimalsCell ProliferationFemaleHumansMiceProspero-Related Homeobox 1 ProteinSignal TransductionHomeodomain ProteinsMicroRNAsMIrn181 microRNA, humanNOTCH1 protein, humanProspero-Related Homeobox 1 ProteinReceptor, Notch1RNA, CircularTumor Suppressor Proteins

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