The transcription factor HBP1 activates ferroptosis in tumor cells by regulating the UHRF1-CDO1 axis

Abstract The induction of ferroptosis in tumor cells is one of the most important mechanisms by which tumor progression can be inhibited; however, the specific regulatory mechanisms underlying ferroptosis remain unclear. In this study, we investigated the important role of HBP1 in ferroptosis. HBP1 down-regulates the protein levels of UHRF1 by inhibiting the expression of the UHRF1 gene at the transcriptional level. Reduced levels of UHRF1 have been shown to regulate the ferroptosis-related gene CDO1 by epigenetic mechanisms, thus up-regulating the level of CDO1 and promoting ferroptosis in tumor cells. On this basis, we constructed metal-polyphenol-network coated HBP1 nanoparticles by combining biological and nanotechnological. MPN-HBP1 nanoparticles entered tumor cells efficiently and innocuously, induced ferroptosis and inhibited the malignant proliferation of tumors by regulating the HBP1-UHRF1-CDO1 signaling pathway. This study provides a new perspective for further research on the regulatory mechanism underlying ferroptosis and its potential role in tumor therapy.