AUTHOR=Sun Kai , Gao Ling , Li Shaoming , Zheng Jingjing , Zhu Zhuang , Zhi Keqian , Ren Wenhao 

TITLE=Circ-CDK8 regulates SLC7A11-mediated ferroptosis by inhibiting miR-615-5p to promote progression in oral squamous cell carcinomas

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1432520

DOI=10.3389/fphar.2024.1432520

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Ferroptosis is a new mode of programmed cell death distinct from necrosis, apoptosis, and autophagy, induced by iron-ion-dependent lipid peroxide accumulation. Circular RNAs are a class of endogenous non-coding RNAs that regulate the biological behavior of tumors. However, the role of circ-CDK8 in regulating ferroptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) remains unknown.</p><p><bold>Methods:</bold> The effect of circ-CDK8 on OSCC cell ferroptosis, migration, and invasion was evaluated using CCK-8, wound healing, transwell, reactive oxygen species (ROS), malondialdehyde (MDA), and GSH assays and Western blotting. Bioinformatics analyses and luciferase reporter assays were performed and revealed targeted relationships between circ-CDK8 and miR-615-5p, miR-615-5p and SLC7A11. Interference with circ-CDK8 expression reduced SLC7A11 expression by sponging miR-615-5p, suppressed OSCC cell migration and invasion, and promoted ferroptosis by increasing ROS, MDA, and iron levels and decreasing GSH and GPX4 levels in OSCC cells. Furthermore, <italic>in vivo,</italic> animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression.</p><p><bold>Results:</bold> Collectively, this study revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC cells via the circ-CDK8/miR-615-5p/SLC7A11 axis, providing new insights into OSCC and a potential therapeutic strategy for OSCC.</p>