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

Liu Yang1, Yin Xiong1, Xian-Feng Hu1

  • 1Department of Geratology, Pu Ai Hospital of Tongji Medical College, Huazhong University of Science and Technology Wuhan 430033, China.

Abstract

Insights

MicroRNA-323 (miR-323) is upregulated in ischemia/reperfusion (I/R) injury, promoting neuronal cell death by targeting BRI3. Inhibiting miR-323 reduces apoptosis and enhances survival in I/R-injured neurons.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Ischemia/reperfusion (I/R) injury is a significant cause of neuronal damage.
  • MicroRNA-323 (miR-323) has been observed to be upregulated in I/R-affected neuronal cells.
  • The precise role and molecular mechanisms of miR-323 in I/R-induced neuronal cell death require elucidation.

Purpose of the Study:

  • To investigate the function of miR-323 in I/R-induced neuronal cell death.
  • To explore the underlying molecular mechanisms by which miR-323 influences neuronal survival and apoptosis.
  • To determine if miR-323 directly targets specific genes involved in I/R injury.

Main Methods:

  • An in vitro oxygen-glucose deprivation (OGD) model was used to simulate I/R injury in rat hippocampal neurons.
  • Cell apoptosis, cell survival rates, and miR-323 expression levels were measured at various time points post-OGD.
  • miR-323 mimics and anti-miR-323 inhibitors were employed to upregulate or downregulate miR-323 expression, respectively.
  • The interaction between miR-323 and BRI3 was assessed, and the effect of BRI3 knockdown on neuronal cells was evaluated.

Main Results:

  • OGD treatment led to increased apoptosis and decreased survival in rat hippocampal neurons.
  • miR-323 expression levels were significantly elevated following OGD exposure.
  • Upregulation of miR-323 exacerbated apoptosis and reduced cell survival, while miR-323 inhibition had the opposite effect.
  • miR-323 was found to directly bind to the 3'-untranslated region (UTR) of BRI3.
  • Knockdown of BRI3 using siRNA resulted in decreased cell survival and increased apoptosis in neurons.

Conclusions:

  • miR-323 plays a critical role in regulating neuronal cell death following ischemia/reperfusion injury.
  • The pro-apoptotic and anti-survival effects of miR-323 in I/R injury are mediated through its direct targeting of BRI3.
  • Targeting miR-323 or its downstream effector BRI3 may represent a therapeutic strategy for mitigating I/R-induced neuronal damage.

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