• Ir J Med Sci · Dec 2022

    Clinical significance and biological effect of ZFAS1 in Hirschsprung's disease and preliminary exploration of its underlying mechanisms using integrated bioinformatics analysis.

    • Yujiao Wang, Peng Cai, and Jian Wang.
    • Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China.
    • Ir J Med Sci. 2022 Dec 1; 191 (6): 266926752669-2675.

    BackgroundThe pathogenesis of Hirschprung's disease (HSCR) remains largely unknown. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) has been found to have vital regulatory roles in a number of diseases. However, the association between ZFAS1 and HSCR has not been reported.AimsThe present study was aimed at investigating the expression pattern and biological function and underlying mechanisms of ZFAS1 in HSCR.MethodsThe expression of ZFAS1 was detected in surgical excision samples of 30 children diagnosed with HSCR and 30 control cases. Functional experiments were conducted after over-expression or knockdown of ZFAS1 in human neuronal cell line SH-SY-5Y. Multiple bioinformatics databases and tools were used to explore the potential regulatory mechanisms of ZFAS1 in HSCR.ResultsCompared with the control group, the HSCR group has a significantly higher level of ZFAS1(P = 0.0012). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.7133 (P = 0.0045), which indicated good biomarker potency of ZFAS1 in HSCR. Functionally, over-expression of ZFAS1 significantly inhibited cell proliferation, whereas knockdown of ZFAS1 promoted cell proliferation and colony formation of SH-SY-5Y cells. Using multiple databases, a competing endogenous RNA (ceRNA) network, containing ZFAS1,13 candidate miRNAs, and 110 potential gene targets, was established. Further enrichment analysis suggested that ZFAS1 may regulate a number of genes and signaling pathways that were crucial for neuron development.ConclusionsOur findings revealed that ZFAS1 may participate in the pathogenesis of HSCR through regulating neuron functions. Bioinformatics analysis highlighted an important perspective for the following mechanical researches.© 2021. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.

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