MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

Ting Zhang1, Hongmei Wang2, Qiang Li3

  • 1Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China549832649@qq.com.

Abstract

Insights

This study investigated MALAT1 and MDM2's role in ischemic stroke via the p53 pathway. Targeting MALAT1/MDM2 reduced cell death and infarct size, suggesting a new therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Genetics

Background:

  • Ischemic stroke is a leading cause of death and disability.
  • The p53 signaling pathway plays a critical role in cellular responses to stress.
  • Long non-coding RNAs (lncRNAs) and their involvement in stroke pathogenesis are increasingly recognized.

Purpose of the Study:

  • To evaluate the effect of MALAT1 and MDM2 on ischemic stroke.
  • To elucidate the regulatory role of MALAT1 and MDM2 in the p53 signaling pathway.
  • To explore the therapeutic potential of targeting the MALAT1/MDM2/p53 axis in ischemic stroke.

Main Methods:

  • Bioinformatics analysis to identify dysregulated lncRNAs, mRNAs, and pathways.
  • In vitro (Oxygen-glucose deprivation/reoxygenation) and in vivo (middle cerebral artery occlusion/reperfusion) models of ischemic stroke.
  • Quantitative real-time PCR (qRT-PCR), Western blot, fluorescence in situ hybridization (FISH), MTT assay, flow cytometry, and immunohistochemistry were employed.

Main Results:

  • MALAT1 and MDM2 were found to be upregulated in ischemic stroke tissues and models.
  • The MALAT1/MDM2/p53 signaling pathway was activated in response to ischemic conditions.
  • Downregulation of MALAT1 and MDM2 promoted cell proliferation, reduced apoptosis, and decreased infarct size in a mouse model of ischemic stroke.

Conclusions:

  • The MALAT1/MDM2/p53 signaling pathway axis is implicated in the pathogenesis of ischemic stroke.
  • Targeting MALAT1 and MDM2 demonstrates a neuroprotective effect, reducing stroke-induced brain damage.
  • This pathway represents a promising therapeutic target for clinical intervention in ischemic stroke patients.

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