EZH2-mediated SLC7A11 upregulation via miR-125b-5p represses ferroptosis of TSCC.

Abstract

Tongue squamous cell carcinoma is one of the most common carcinomas in oral cancer with a high morbidity and mortality. Ferroptosis is a novel type of cell death involved in various diseases including cancers. Additionally, Enhancer of Zeste homolog 2 (EZH2) is significantly associated with a poor prognosis in esophageal squamous cell carcinoma patients but its role in TSCC is unclear. In this study, we tried to investigate the possible mechanism of EZH2 involved in the ferroptosis of TSCC. Expression of EZH2 and SLC7A11 was determined by RT-qPCR. CCK-8 assays were performed to quantify the cell death rate of TSCC cells. Malondialdehyde (MDA) assays were performed to quantify the lipid accumulation. Western blot was performed to analyze the expression level of SLC7A11. We used dual-luciferase reporter assays to determine the association between EZH2 and miR-125b-5p promoter, and miR-125b-5p and the SLC7A11 3' untranslated region (UTR). Overexpression of EZH2 and SLC7A11 inhibits erastin-induced ferroptosis in TSCC cells. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11. EZH2 inhibits the ferroptosis of TSCC cells by inhibiting miR-125b-5p and enhancing SLC7A11. EZH2 inhibits erastin-induced ferroptosis in TSCC cells via miR-125b-5p/SLC7A11 axis.