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 mechanism underlying ferroptosis remains unclear. In this study, we found that transcription factor HBP1 has a novel function of reducing the antioxidant capacity of tumor cells. 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 increasing the sensitivity of hepatocellular carcinoma and cervical cancer cells to ferroptosis. 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 axis. This study provides a new perspective for further research on the regulatory mechanism underlying ferroptosis and its potential role in tumor therapy.
Funder
National Natural Science Foundation of China
Beijing Natural Science Foundation Grant
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Cited by
1 articles.
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