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The flux through the HBP elevated the global O-GlcNAcylation level and led to the activation of survival signaling pathways in HCC cells. Furthermore, GFPT1 was proved to be an important downstream regulator of FOXA2-mediated apoptotic suppression. These results provide insights into the molecular mechanism by which FOXA2 inhibits DOX-induced HCC cell apoptosis and suggest that targeting FOXA2 might offer a new strategy for HCC treatment.Fragile X-related protein 1 (FXR1) is an RNA-binding protein that can regulate specific mRNA decay