HOXA5 Inhibits Microglia Pyroptosis in Cerebral Stroke by Regulating FTO ‐Mediated TMEM59 m 6 A Demethylation

Microglia pyroptosis promotes neuroinflammation and secondary brain injury in cerebral stroke. Herein, the role of homeoboxA5 (HOXA5) in regulating microglia pyroptosis during the development of cerebral stroke was studied. Cerebral stroke models were established by MCAO and OGD/R treatment. TTC staining and FJB staining were used to assess cerebral infarction size and neuronal damage. The pathogenic alterations in brain tissues were analyzed by HE staining. MTT and flow cytometry assays were used to determine cell viability and pyroptosis, respectively. TMEM59 m⁶A level was examined using MeRIP assay. The interaction between HOXA5 and FTO was analyzed by dual luciferase reporter gene and ChIP assays. The interaction between YTHDF2 and TMEM59 was investigated using RIP assay. HOXA5 was lowly expressed in cerebral stroke. HOXA5 overexpression reduced MCAO-induced cerebral injury in rats. HOXA5 upregulation inhibited MCAO and OGD/R-induced microglia pyroptosis. HOXA5 transcriptionally activated FTO expression in microglia. FTO overexpression prevented TMEM59 mRNA degradation by reducing YTHDF2-mediated m⁶A recognition. HOXA5 overexpression inhibited microglia pyroptosis in cerebral stroke by regulating FTO-mediated TMEM59 mRNA m⁶A modification.