Downregulation of circ_008018 protects against cerebral ischemia-reperfusion injury by targeting miR-99a

Biochem Biophys Res Commun. 2018 May 23;499(4):758-764. doi: 10.1016/j.bbrc.2018.03.218. Epub 2018 Apr 4.

Abstract

Circular RNAs (circRNAs) are highly expressed in eukaryotic cells and regulate physiological and pathophysiological processes. However, the role of circRNAs in cerebral ischemia-reperfusion (I/R) injury remains largely unknown. In this study, we found that circ_008018 level was higher in the cortical tissue of mice with middle cerebral artery occlusion as compared to those in the sham group 24 h after reperfusion. Knockdown of circ_008018 attenuated cerebral I/R-induced brain tissue damage and neurological deficits in mice by inducing microRNA miR-99a overexpression. The decreased phosphorylation of Akt and glycogen synthase kinase 3β caused by I/R was partly reversed by circ_008018 silencing or miR-99a overexpression. Taken together, these results provide new insight into the mechanisms of apoptosis resulting from cerebral I/R injury and suggest that targeted inhibition of circ_008018 can protect against subsequent neurological damage.

Keywords: Cerebral ischemia-reperfusion injury; Circular RNAs; circ_008018; miR-99a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Brain Ischemia / prevention & control*
  • Down-Regulation / genetics*
  • Gene Silencing
  • Glycogen Synthase Kinase 3 beta / genetics
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Circular
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction

Substances

  • MicroRNAs
  • Mirn99 microRNA, mouse
  • RNA, Circular
  • RNA
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt