Circ_STIL Affects Ferroptosis by Sponging miR ‐338‐3p in Oral Squamous Cell Carcinoma

Background Ferroptosis is pivotal in cancer onset and progression, which can be mediated by non‐coding RNAs. Objectives This study examined the expression profile of circSTIL/miR‐338‐3p in oral squamous cell carcinoma (OSCC) patients. Its regulatory mechanism in ferroptosis and OSCC cells was also examined. Materials and Methods Fifty OSCC tissue samples were collected to profile gene expression and validate clinical relevance. Functional assays in OSCC cell lines explored how circSTIL and miR‐338‐3p modulation affect proliferation and migration. Ferroptosis was assessed by quantifying intracellular Fe 2+ , ROS, and MDA, while ferroptosis‐related key proteins' levels were measured via western blot. Potential target genes were predicted via online databases, with their functions and pathways analyzed using GO and KEGG enrichment analysis. Results circSTIL was significantly upregulated in OSCC tumor samples, with its expression levels correlated with tumor size, lymph node metastasis status, and histological grade. Knockdown of circSTIL notably impaired the migratory and invasive capacities of OSCC cells, concurrently initiating ferroptotic cell death. Mechanistically, circSTIL functions as a sponge for miR‐338‐3p. Silencing miR‐338‐3p partially reversed the role of si‐circSTIL against the malignant behavior of tumor cells, with GPX4 as its direct target. Conclusion circSTIL/miR‐338‐3p axis plays a key role in the malignant progression of OSCC and ferroptosis. GPX4 may function as the key target in this regulatory network.