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Downregulation of circular RNA HECTD1 induces neuroprotection against ischemic stroke through the microRNA-133b/TRAF3

Quande Dai1, Yu Ma1, Zhonghai Xu1

  • 1Department of Neurology, The First People's Hospital of Shangqiu, No. 292 South Kaixuan Road, Suiyang District, Shangqiu City 476100, Henan Province, PR China.

Life Sciences
|November 5, 2020
PubMed

Insights

Circular RNA HECTD1 (circ-HECTD1) exacerbates brain injury after stroke by targeting miR-133b and increasing TRAF3 expression. Reducing circ-HECTD1 offers a potential therapeutic strategy for ischemic stroke by protecting neurons.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Genetics

Background:

  • Circular RNAs (circRNAs) are critical in biological processes and diseases.
  • The role of circRNAs in ischemic stroke is not fully understood.
  • This study investigates circRNA HECTD1 (circ-HECTD1) in cerebral ischemia/reperfusion injury.

Purpose of the Study:

  • To explore the functional role of circ-HECTD1 in cerebral ischemia/reperfusion injury.
  • To elucidate the underlying mechanism of circ-HECTD1 in this process.
  • To identify potential therapeutic targets for ischemic stroke.

Main Methods:

  • Established mouse middle cerebral artery occlusion (MCAO) and HT22 cell oxygen-glucose deprivation (OGD) models.
  • Assessed brain infarct volume, apoptosis, and inflammatory markers (caspase 3, NF-κB).
  • Utilized luciferase reporter assays to determine molecular interactions.

Main Results:

  • circ-HECTD1 and TRAF3 were upregulated, while miR-133b was downregulated in ischemia models.
  • Knockdown of circ-HECTD1 reduced neuronal death, infarct volume, and apoptosis.
  • circ-HECTD1 negatively regulated miR-133b, which targets TRAF3; miR-133b inhibited OGD-induced apoptosis and NF-κB activation.

Conclusions:

  • circ-HECTD1 knockdown mitigates neuronal injury in cerebral ischemia by inhibiting TRAF3 via targeting miR-133b.
  • circ-HECTD1 inhibition represents a promising therapeutic avenue for ischemic stroke.
  • The circ-HECTD1/miR-133b/TRAF3 axis is a key regulator of ischemic brain injury.
Abstract

Keywords:
Circular RNAHECTD1MicroRNA-133bNeuroprotectionTumor necrosis factor receptor–associated factor 3

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