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

Pediatr Surg Int. 2020 Aug;36(8):883-890. doi: 10.1007/s00383-020-04686-0. Epub 2020 Jun 7.

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.

Keywords: Apoptosis; EGR2; Hirschsprung’s disease; SH-SY5Y; miR-140-5p.

MeSH terms

  • Blotting, Western
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation / genetics
  • Down-Regulation / physiology*
  • Early Growth Response Protein 2 / genetics
  • Early Growth Response Protein 2 / metabolism*
  • Female
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / metabolism
  • Hirschsprung Disease / pathology*
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Real-Time Polymerase Chain Reaction

Substances

  • EGR2 protein, human
  • Early Growth Response Protein 2
  • MicroRNAs
  • Mirn140 microRNA, human