Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Cerebral infarction (CI) leads to significant neuronal damage.
• Angiogenesis plays a critical role in recovery after CI.
• The role of long non-coding RNAs (lncRNAs) in CI-induced angiogenesis is not fully understood.

Purpose of the Study:

• To investigate the mechanism of lncRNA MEG3 in regulating angiogenesis following cerebral infarction.
• To elucidate the role of MEG3 in protecting brain microvascular endothelial cells (RBMVECs) from oxygen-glucose deprivation/reoxygenation (OGD/R) injury.
• To explore the interaction between MEG3, p53, and NOX4 in the context of CI.

Main Methods:

• Established a CI model using rat brain microvascular endothelial cells (RBMVECs) subjected to OGD/R.
• Quantified gene and protein expression using RT-qPCR and Western blot.
• Assessed cell apoptosis and reactive oxygen species (ROS) generation via flow cytometry.
• Determined cell viability using the MTT assay.
• Investigated molecular interactions using RNA-immunoprecipitation (RIP) and chromatin co-immunoprecipitation (CHIP) assays.

Main Results:

• OGD/R increased MEG3 and NOX4 expression in RBMVECs, showing a positive correlation.
• Knockdown of MEG3 protected RBMVECs from OGD/R-induced apoptosis, decreased NOX4 and p53 expression, enhanced pro-angiogenic factors (HIF-1α, VEGF), and reduced ROS.
• RIP and CHIP assays confirmed MEG3 interacts with p53, and p53 binds to NOX4 promoters, indicating MEG3 regulates NOX4 via p53.
• Knockdown of NOX4 also protected RBMVECs, increasing viability and pro-angiogenic factors while reducing ROS.

Conclusions:

• LncRNA MEG3 acts as a key regulator in OGD/R-induced RBMVEC apoptosis.
• The mechanism involves MEG3 modulating the p53/NOX4 axis to reduce ROS generation, thereby influencing angiogenesis after CI.