Title : O GlcNAcylation enhances sensitivity to RSL3 induced ferroptosis via the YAP TFRC pathway in liver cancer
Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid hydroperoxide to lethal levels. YAP has been reported to play a pivotal role in controlling ferroptotic death, and the expression of YAP is enhanced and stabilized by O-GlcNAcylation. However, whether O-GlcNAcylation can increase the sensitivity of hepatocellular carcinoma (HCC) cells to ferroptosis remains unknown. In the present study, we found that OGlcNAcylation increased the sensitivity of HCC cells to ferroptosis via YAP. Moreover, YAP increased the iron concentration in HCC cells through transcriptional elevation of TFRC via its O-GlcNAcylation. With YAP knockdown or YAP-T241 mutation, the increased sensitivity to ferroptosis induced by O-GlcNAcylation was abolished. In addition, the xenograft assay confirmed that O-GlcNAcylation increased ferroptosis sensitivity via TFRC in vivo. In summary, we are the first to find that O-GlcNAcylation can increase ferroptosis sensitivity in HCC cells via YAP/TFRC. Our work will provide a new basis for clinical therapeutic strategies for HCC patients.
What will audience learn from your presentation?
- This work will help the audience and researches in development their researches and can use to expand their research or teaching, provide a practical solution to a problem that could simplify.
- Explore the treatments of Tumors and will open a prospects for a new development in science and medicine
- Our work also will provide a new basis for clinical therapeutic strategies for HCC patients.