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

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Abstract

Background

The 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.

Aims

The present study was aimed at investigating the expression pattern and biological function and underlying mechanisms of ZFAS1 in HSCR.

Methods

The 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.

Results

Compared 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.

Conclusions

Our 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.

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Availability of data and material

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

This research project was supported by the Science Foundation of Suzhou Science and Technology Bureau (grant no. SYS2020158).

Funding

This study was supported by the Natural Science Foundation of China (NSFC 82100534) and the Science Foundation of Suzhou Science and Technology Bureau (SYS 2020158).

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Authors and Affiliations

  1. Department of Pediatric Surgery, Children’s Hospital of Soochow University, Suzhou, China

    Yujiao Wang, Peng Cai & Jian Wang

Authors
  1. Yujiao Wang
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  2. Peng Cai
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  3. Jian Wang
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Contributions

All the authors contributed to the study conception and design, data collection and analysis. The first draft of the manuscript was written by Y. W., and revised by P. C. and J. W. All the authors approved the final manuscript.

Corresponding author

Correspondence to Jian Wang.

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Ethics approval

This study was approved by the Ethics Committee of Children’s Hospital of Soochow University, and conducted in compliance with the principles of the Helsinki Declaration.

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Informed consent was obtained from the legal guardians of each child included in the study.

Consent for publication

Informed consent regarding data publishing was obtained from the legal guardians of each child.

Conflict of interest

The authors declare no competing interests.

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Wang, Y., Cai, P. & Wang, J. Clinical significance and biological effect of ZFAS1 in Hirschsprung’s disease and preliminary exploration of its underlying mechanisms using integrated bioinformatics analysis. Ir J Med Sci 191, 2669–2675 (2022). https://doi.org/10.1007/s11845-021-02906-7

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  • DOI: https://doi.org/10.1007/s11845-021-02906-7

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