简介：铁死亡是一种不同于坏死、凋亡和自噬的新的程序性细胞死亡模式，由铁离子依赖性脂质过氧化物积累诱导。环状RNA是一类调节肿瘤生物学行为的内源性非编码RNA。然而，circ-CDK8 在调节口腔鳞状细胞癌 (OSCC) 铁死亡、迁移和侵袭中的作用仍不清楚。方法：使用 CCK-8、伤口愈合、Transwell、活性氧 (ROS)、丙二醛 (MDA) 和 GSH 测定以及蛋白质印迹法评估 circ-CDK8 对 OSCC 细胞铁死亡、迁移和侵袭的影响。进行生物信息学分析和荧光素酶报告基因测定，揭示了 circ-CDK8 与 miR-615-5p、miR-615-5p 和 SLC7A11 之间的靶向关系。干扰 circ-CDK8 表达可通过海绵 miR-615-5p 降低 SLC7A11 表达，抑制 OSCC 细胞迁移和侵袭，并通过增加 OSCC 细胞中 ROS、MDA 和铁水平以及降低 GSH 和 GPX4 水平促进铁死亡。此外，在体内，动物实验证实circ-CDK8干扰抑制OSCC细胞增殖和SLC7A11表达。结果：总的来说，这项研究揭示了一种通过 circ-CDK8/miR-615-5p/SLC7A11 轴上调erastin诱导的 OSCC 细胞铁死亡的新策略，为 OSCC 提供了新的见解和 OSCC 的潜在治疗策略。版权所有 © 2024孙、高、李、郑、朱、智、任。

Introduction: 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. Methods: 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, in vivo, animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression. Results: 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.Copyright © 2024 Sun, Gao, Li, Zheng, Zhu, Zhi and Ren.