Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's disease

J Cell Physiol. 2019 Jul;234(7):10576-10587. doi: 10.1002/jcp.27733. Epub 2018 Nov 15.

Abstract

It has been suggested that circular RNAs play critical roles in natural growth and disease development. Nevertheless, whether the circular RNAs were related in Hirschsprung's disease (HSCR) remains unknown. Thus, we discovered the cir-CCDC66 was downregulated in HSCR compared with the normal gut tissues. The cir-CCDC66 reduction might inhibit cells' proliferation and migration in vitro. Then, we found that DCX transcript was putative cir-CCDC66 competing endogenous RNA. Furthermore, the function of cir-CCDC66 as a sponge for miR-488-3p to regulate DCX RNA expression was demonstrated by immunoprecipitation and luciferase reporter assays. In conclusion, this is the first report revealing that cir-CCDC66 modulates DCX expression through sponging miR-488-3p and thus participates in the onset of HSCR.

Keywords: Hirschsprung's disease; circular RNA; competing endogenous RNAs; neuronal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Eye Proteins / genetics*
  • Female
  • Gene Expression Regulation / genetics
  • HEK293 Cells
  • Hirschsprung Disease / genetics*
  • Hirschsprung Disease / pathology
  • Humans
  • Infant
  • Male
  • MicroRNAs / genetics*
  • Microtubule-Associated Proteins / genetics*
  • Neuropeptides / genetics*
  • RNA, Circular / genetics*
  • RNA-Binding Proteins / genetics

Substances

  • CCDC66 protein, human
  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Eye Proteins
  • MIRN488 microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Neuropeptides
  • RNA, Circular
  • RNA-Binding Proteins