MicroRNA-323 regulates ischemia/reperfusion injury-induced neuronal cell death by targeting BRI3

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10725-33. eCollection 2015.

Abstract

Purpose: MicroRNA-323 (miR-323) has been reported to be upregulated in Ischemia/Reperfusion (I/R) injury-treated neuronal cell. However, the effect and underlying mechanism of miR-323 in I/R-induced neuronal cell death remains poorly understood. The current study was aim to investigate the role and molecular basis of miR-323 in I/R-induced neuronal cell.

Methods: An oxygen-glucose deprivation (OGD) model of hippocampal neuron I/R was produced in vitro. Cell apoptosis, cell survival, and the expression of miR-323 were determined after 6 h, 12 h and 24 h after OGD treatment. The up- or down-regulation of miR-323 was performed by miR-323 mimics or anti-miR-323, respectively.

Results: OGD induced apoptosis and suppressed survival in rat hippocampal neurons. And the expression levels of miR-323 were increased after OGD treatment. Furthermore, the up-regulation of miR-323 promoted apoptosis and suppressed survival, whereas the inhibition of miR-323 suppressed apoptosis and enhanced survival in OGD-treated neurons. Moreover, miR-323 could directly bind to BRI3 3'-UTR. Notably, the knockdown of BRI3 by BRI3 siRNA apparently abrogated cell survival and induced cell apoptosis in rat neurons.

Conclusion: This study indicated that miR-323 might regulate ischemia/reperfusion-induced rat neuronal cell death via targeting BRI3.

Keywords: BRI3; MicroRNA-323; ischemia/reperfusion injury; neuronal apoptosis.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Animals, Newborn
  • Apoptosis
  • Binding Sites
  • Cell Death
  • Cell Hypoxia
  • Cells, Cultured
  • Gene Expression Regulation
  • Glucose / deficiency
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nerve Degeneration*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxygen / metabolism
  • RNA Interference
  • Rats, Sprague-Dawley
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control
  • Time Factors
  • Transfection

Substances

  • 3' Untranslated Regions
  • BRI3 protein, rat
  • MIRN323 microRNA, rat
  • Membrane Proteins
  • MicroRNAs
  • Nerve Tissue Proteins
  • Glucose
  • Oxygen