METTL3-Mediated m6A Modification of lncRNA-0949 Drives Microglial Inflammation in an vitro Model of Sepsis-Associated Encephalopathy.

Introduction: Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis with limited therapeutic options. Although neuroinflammation driven by microglial activation is central to SAE pathogenesis, the underlying epitranscriptional regulatory mechanisms remain poorly defined. Here, we investigated the role of the m Methods: HMO6 cells were stimulated with LPS (1 μg/mL) for 0-24 h to establish an SAE model. METTL3 expression was assessed by Western blotting and immunofluorescence. MeRIP-qPCR was used to detect m Results: LPS stimulation time-dependently increased oxidative stress (MDA), pro-inflammatory cytokines (MIP-2, IL-1β, TNF-α, IL-6), and METTL3 protein expression (2.99-fold at 24 h, P < 0.001). METTL3 catalyzed m Conclusion: Together, these findings define a METTL3-m6A-lncRNA-0949 regulatory axis that amplifies microglial inflammation in an in vitro SAE model. This study provides the first evidence that METTL3-driven m6A modification of lncRNA-0949 contributes to neuroinflammation, offering a new mechanistic perspective and highlighting the need for in vivo validation to assess therapeutic potential.