FTO-mediated m6A modification of FTH1 inhibits ferroptosis of neurons in neonatal cerebral hypoxic ischaemia

FTO is aberrantly expressed in brain disorders. However, the roles of FTO in neonatal hypoxic-ischemic brain injury (HIE) are still unclear. This study aims to investigate the potential of FTO in neonatal HIE. Oxygen-glucose deprivation (OGD) was used to establish HIE in vitro. mRNA levels were detected by RT-qPCR. Protein expression was detected by western blot. The levels of MDA, SOD, Fe2+ and GSH was detected by specific kit. m6A sites were analyzed using SRAMP and further verify by MeRIP assay. Cell proliferation was determined by CCK-8. Cell death was determined by PI staining. FTO was downregulated in patients with neonatal HIE and OGD-treated neurons. Moreover, FTO mRNA expression was decreased in ferroptosis inducer, especially FAC. However, overexpression of FTO inhibited the ferroptosis of neurons. Moreover, FTO-mediated m6A modification of FTH1 suppressed its mRNA expression and stability, inhibiting its protein expression. However, overexpression of FTH1 abrogated the effects of FTO and promoted the ferroptosis of neurons. In summary, FTO functions as a protective role in neonatal HIE via inhibiting FTH1 signaling. Thence, targeting may be a promising strategy for FTO neonatal HIE.