Hsa_circ_0007534/miR-761/ZIC5 regulatory loop modulates the proliferation and migration of glioma cells

Biochem Biophys Res Commun. 2018 May 23;499(4):765-771. doi: 10.1016/j.bbrc.2018.03.219. Epub 2018 Apr 10.

Abstract

Increasing evidences demonstrate the essential roles of circular RNAs (circRNAs) in human cancers. However, the study about the functions of circRNAs in glioma remains very limited. In the present study, we found that circRNA hsa_circ_0007534 was highly expressed in glioma tissues compared to normal brain tissues. Furthermore, we found that knockdown of hsa_circ_0007534 significantly inhibited the proliferation and migration of glioma cells. In mechanism, we showed that hsa_circ_0007534 could sponge miR-761 to repress its availability in glioma cells. We found that inhibition of miR-761 could rescue the suppressed proliferation and migration of glioma cells by hsa_circ_0007534 knockdown. Moreover, we explored the downstream mechanism and found that ZIC5 was a target of miR-761. We showed that hsa_circ_0007534 promoted the expression of ZIC5 by inhibiting miR-761 in glioma cells. And restoration of ZIC5 expression significantly reversed the effects of hsa_circ_0007534 knockdown on glioma cell proliferation and migration. In summary, our results demonstrated that hsa_circ_0007534 serves as an oncogene in glioma via promoting ZIC5 expression by repressing miR-761 availability. Our results suggested that hsa_circ_0007534/miR-761/ZIC5 regulatory loop might be a promising therapeutic target for glioma treatment.

Keywords: Glioma; Migration; Proliferation; hsa_circ_0007534; miR-761.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • DNA-Binding Proteins
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Circular
  • Signal Transduction*
  • Transcription Factors / metabolism*
  • Up-Regulation / genetics

Substances

  • DNA-Binding Proteins
  • MicroRNAs
  • RNA, Circular
  • Transcription Factors
  • ZIC5 protein, human
  • microRNA761 microRNA, human
  • RNA