N6-methyladenosine reader YTHDF3-mediated Lcn2 mRNA stability promotes the hepatotoxicity of crizotinib

The liver injury induced by crizotinib is an urgent clinical problem to be solved. Therefore, exploring the mechanism of crizotinib-induced liver injury is crucial to finding prevention and treatment methods. The mouse and cell models of crizotinib-induced liver injury were established in this study. RNA-sequencing, N6-methyladenosine methylated RNA immunoprecipitation-sequencing, and MeRIP-qPCR were performed to identify the target gene. The upregulation of target gene was confirmed in vitro and in vivo models. Further mechanistic study was performed by knockdown or overexpression of the related gene. Our study found that the m6A reading protein YTHDF3-Lcn2-apoptosis axis plays a critical role in mediating the hepatotoxicity of crizotinib, which provides potential intervention approaches for alleviating crizotinib-induced liver injury.