MiR-298 Exacerbates Ischemia/Reperfusion Injury Following Ischemic Stroke by Targeting Act1

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Ischemic stroke is a leading cause of death and disability worldwide.
• MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in various pathological processes, including stroke.
• The specific role of miR-298 in ischemic stroke pathogenesis remains largely unexplored.

Purpose of the Study:

• To investigate the role of miR-298 and its target Act1 in ischemic stroke.
• To elucidate the molecular mechanisms underlying miR-298-mediated regulation of Act1 in the context of ischemic stroke.
• To evaluate the therapeutic potential of targeting miR-298 for ischemic stroke treatment.

Main Methods:

• Quantitative real-time PCR and western blotting were used to assess miR-298 and Act1 expression.
• Luciferase assays confirmed the direct binding of miR-298 to the Act1 3' untranslated region.
• In vitro and in vivo models of ischemic stroke, including middle cerebral artery occlusion and short interfering RNA-mediated knockdown of Act1, were employed.

Main Results:

• miR-298 was downregulated, while Act1 was upregulated in ischemic stroke.
• miR-298 overexpression suppressed Act1 levels and exacerbated brain injury, including increased apoptosis, autophagy, infarction, and neurological deficits.
• These effects were mediated by the inhibition of the Act1/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB signaling pathway and downstream autophagy.

Conclusions:

• Upregulation of miR-298 promotes brain injury in ischemic stroke by inhibiting the Act1/JNK/NF-κB signaling cascade and autophagy.
• Targeting miR-298 presents a potential therapeutic strategy for managing ischemic stroke.