RETRACTED: MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs) are implicated in human diseases, including ischemic stroke.
• miR-378 is downregulated in ischemic stroke models and its expression can be modulated by hypoxic preconditioning.
• Caspase-3 is a critical executioner of apoptosis, playing a significant role in ischemic brain injury.

Purpose of the Study:

• To investigate the role of miR-378 in ischemic brain injury.
• To determine the molecular mechanism by which miR-378 affects ischemic injury, specifically its interaction with Caspase-3.
• To evaluate the therapeutic potential of miR-378 in an ischemic stroke model.

Main Methods:

• Oxygen-glucose deprivation (OGD) in N2A cells to mimic ischemic conditions.
• Overexpression and downregulation of miR-378 using mimics and inhibitors.
• Bioinformatic analysis to predict miR-378 targets.
• Luciferase reporter assay to confirm direct binding of miR-378 to Caspase-3.
• Middle cerebral artery occlusion (MCAO) mouse model to assess in vivo effects.
• Western blot analysis for protein expression levels (e.g., cleaved-caspase-3).

Main Results:

• miR-378 levels decreased in N2A cells after OGD.
• Overexpression of miR-378 enhanced cell viability and reduced apoptosis markers (TUNEL, cleaved-caspase-3) following OGD.
• Downregulation of miR-378 exacerbated OGD-induced apoptosis.
• miR-378 directly targets and represses the translation of Caspase-3 mRNA.
• In vivo, miR-378 agomir reduced infarct volume and neural cell death in MCAO mice.
• Caspase-3 knockdown reversed the neuroprotective effects of anti-miR-378.

Conclusions:

• miR-378 exerts neuroprotective effects against ischemic injury.
• The mechanism involves the direct negative regulation of Caspase-3 by miR-378.
• miR-378 represents a promising therapeutic target for treating ischemic stroke.