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Preliminary identification of key miRNAs, signaling pathways, and genes associated with Hirschsprung’s disease by analysis of tissue microRNA expression profiles

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Abstract

Background

Hirschsprung’s disease (HSCR) is a congenital gut motility disorder of infants, and if left untreated, it is fatal to the affected infants. This study aimed to identify key microRNAs (miRNAs), signaling pathways and genes involved in the pathogenesis of HSCR.

Methods

The miRNA microarray dataset GSE77296 was downloaded. Nine colon tissue samples were available: six from HSCR patients and three matched control samples. Differentially expressed miRNAs (DEMs) were identified after data preprocessing. Target genes of the selected upregulated and downregulated DEMs were predicted. In addition, functional enrichment analyses for the selected DEMs and target genes were conducted. Finally, interaction networks between the DEMs and target genes were constructed.

Results

A total of 162 DEMs (73 upregulated and 89 downregulated) were obtained. A total of 2511 DEM-target gene pairs for the 40 selected DEMs were identified, including 1645 pairs for the upregulated DEMs and 866 pairs for the downregulated DEMs. The upregulated DEM miR-141-3p and down-regulated DEM miR-30a-3p were identified as key miRNAs by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses. Besides, KEGG pathway enrichment analysis revealed that pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway were key pathways. The key genes frizzled class receptor 3 (FZD3) and docking protein 6 (DOK6) were obtained through the DEM-target gene interaction networks.

Conclusion

Two key miRNAs (miR-141-3p and miR-30a-3p), the MAPK signaling pathway and two key genes (FZD3 and DOK6) were implicated in the pathogenesis of HSCR.

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Authors and Affiliations

  1. Pediatric General Surgery Department, The Children’s Hospital, Zhejiang University School of Medicine, 3333 Binsheng Road, Hangzhou, 310052, China

    Zhi-Gang Gao, Qing-Jiang Chen, Yun-Zhong Qian, Li-Feng Zhang, Yue-Bin Zhang & Qi-Xing Xiong

  2. International Medical Center, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China

    Min Shao

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  1. Zhi-Gang Gao
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  2. Qing-Jiang Chen
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  3. Min Shao
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  4. Yun-Zhong Qian
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  5. Li-Feng Zhang
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Corresponding author

Correspondence to Yun-Zhong Qian.

Additional information

Funding: This work was supported by Chinese Medical Bureau of Zhejiang Province (2011ZA068), Science and Technology Project of Zhejiang Province (2017KY441), and Health and Family Planning Commission of Zhejiang Province (11-CX23).

Ethical approval: The dataset used in this study is downloaded from GEO database. Our study is not involved in animal or human experiment, so there is no ethical approval.

Competing interest: None.

Contributors: Gao ZG wrote the first draft of this paper, all authors contributed to the intellectual content and approved the final version of the manuscript.

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Gao, ZG., Chen, QJ., Shao, M. et al. Preliminary identification of key miRNAs, signaling pathways, and genes associated with Hirschsprung’s disease by analysis of tissue microRNA expression profiles. World J Pediatr 13, 489–495 (2017). https://doi.org/10.1007/s12519-017-0064-z

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  • DOI: https://doi.org/10.1007/s12519-017-0064-z

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