FBXW7 promotes ferroptosis in head and neck squamous cell carcinoma cells through inhibiting c-Myc/SOX2/SLC7A11

Abstract

Objective To explore the effect of FBXW7 on ferroptosis in head and neck squamous cell carcinoma. Methods Head and neck squamous cell lines HN4 and HN6 were cultured in vitro. FBXW7 and SOX2 overexpression plasmids were constructed, and the plasmids were stably transfected into cell lines. The overexpression transfection efficiency was verified at the transcription level and protein level by qRT-PCR and Western blot experiments, respectively. The lipid peroxidation levels of head and neck squamous cell carcinoma cells with overexpressing FBXW7 were verified by measuring malondialdehyde(MDA), glutathione(GSH), and reactive oxygen species(ROS) levels. After treating cells with ferroptosis inhibitor Fer-1, the changes in cell viability were further detected to verify the effect of FBXW7 on ferroptosis. The effect of transfection of the overexpressed plasmid on cellular pathways was detected by Western blot. Results HN4 and HN6 cell lines showed increased levels of lipid peroxidation after overexpression of FBXW7, and the ferroptosis inhibitor Fer-1 was able to effectively reverse the ferroptosis induced by overexpression of FBXW7. Western blot assay results showed that overexpression of FBXW7 reduced the expression of c-Myc, SOX2 and SLC7A11. Conclusion FBXW7 regulates the expression of SOX2-SLC7A11 by degrading c-Myc, thereby effectively regulating ferroptosis in HNSCC.

Keywords

• |head and neck squamous cell carcinoma|fbxw7|ferroptosis|sox2