Downregulation of miR-140-5p affects the pathogenesis of HSCR by targeting EGR2

Abstract

Background/aims

Hirschsprung's disease (HSCR) is the most common digestive disease caused by disorders of neural crest development. Despite the known involvement of miR-140-5p in many human diseases, its biological role in Hirschsprung’s disease (HSCR) remains undefined. In this study, we sought to reveal the roles of miR-140-5p in the pathogenesis of HSCR.

Methods

Quantitative real-time PCR and western blotting were used to measure the relative expression levels of miRNAs, mRNAs, and proteins in stenotic and dilated sections of the colon of 32 HSCR patients. Targets and proteins were evaluated by western blotting, and Transwell, CCK-8, and flow cytometry assays were adopted to detect the functional effects of miR-140-5p on SH-SY5Y cells.

Results

miR-140-5p was significantly downregulated in HSCR tissue samples with increased expression of EGR2, and knockdown of miR-140-5p inhibited cell migration and proliferation and promoted apoptosis in SH-SY5Y cell lines. EGR2 expression was inversely correlated with that of miR-140-5p in cell lines.

Conclusions

miR-140-5p may influence the pathogenesis of HSCR by targeting EGR2.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.

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Funding

Thanks are given for the funding provided by the National Natural Science Foundation (81400575), the Hunan Provincial Natural Science Foundation of China (Grant no. 2017JJ4071), the Science and Technology Development Plan Project of Shandong Province, China (2014GSF118144, 2018GSF118209, 2019GSF108061), the Jinan Science and Technology Bureau (201907003) and the Shandong Provincial Natural Science Foundation (ZR2017MH091, ZR2015HM048).

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Authors

Contributions

GQD and XQW conceived and designed the study. GQD, YDW and YFZ contributed to the work by designing and performing the experiments, collecting and analyzing data, and drafting the manuscript. WL and RDW read and approved the final manuscript.

Corresponding authors

Correspondence to Wei Liu or Rongde Wu.

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Conflict of interest

All the authors declare that they have no competing interests.

Ethical statement

The study was approved by the Ethics Committee of the Provincial Hospital affiliated to Shandong University, with the approval number 2019-179. The guardians of all included patients provided informed consent for the use of their specimens, and the privacy of each child was strictly confidential. The research process is consistent with the principles of the Declaration of Helsinki.

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Not applicable.

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Cite this article

Du, G., Wang, X., Wu, Y. et al. Downregulation of miR-140-5p affects the pathogenesis of HSCR by targeting EGR2. Pediatr Surg Int 36, 883–890 (2020). https://doi.org/10.1007/s00383-020-04686-0

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Keywords

  • EGR2
  • Hirschsprung’s disease
  • SH-SY5Y
  • Apoptosis
  • miR-140-5p