METTL3 inhibition alleviates neuroinflammation and apoptosis by reducing ETV4 m6A modification.

ABSTRACT: Intracerebral hemorrhage (ICH) triggers devastating secondary brain injury driven by maladaptive microglial activation and neuroinflammation. While N6-methyladenosine (m6A) RNA methylation influences inflammation, its spatiotemporal regulation in ICH microglia remains unclear. Here, we identified METTL3 as a key epigenetic driver that promotes neuropathology post-ICH. Our analyses revealed that upregulated METTL3 expression in activated microglia in ICH model mice was correlated with increased global m6A levels. Functional studies have demonstrated that METTL3 depletion attenuates the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), suppresses NF-κB activation, and reduces apoptosis in microglia. Mechanistically, MeRIP-seq and RNA-seq identified the transcription factor ETV4

SUBMITTER: He D 

PROVIDER: S-EPMC12832542 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature