YY1 Induced FOXD2 ‐ AS1 Drives Proliferation of Oral Squamous Cell Carcinoma Through EZH2 / CDKN1A Axis

Introduction Long non‐coding RNAs ( lncRNAs ) have gained recognition as pivotal regulators in cancer biology. Among them, FOXD2 ‐ AS1 has been implicated in multiple cancer types; however, its functional significance and regulatory mechanisms in oral squamous cell carcinoma ( OSCC ) remain unclear. This study explores the mechanism of FOXD2 ‐ AS1 in OSCC progression, focusing on its interaction with the EZH2 / CDKN1A axis. Materials and Methods FOXD2 ‐ AS1 expression was analyzed in TCGA datasets and clinical OSCC samples, validated by qRT ‐ PCR / FISH . Functional impacts on proliferation, cell cycle (flow cytometry) and apoptosis were assessed. Mechanistic studies employed ChIP / RIP /dual‐luciferase assays for FOXD2 ‐ AS1 / YY1 / EZH2 interactions, with xenograft models evaluating tumorigenicity. Results FOXD2 ‐ AS1 was markedly upregulated in OSCC tissues and linked to poor prognosis. Its knockdown suppressed proliferation, induced G1 arrest, and promoted apoptosis, while overexpression reversed these effects. Mechanistically, YY1 transcriptionally activated FOXD2 ‐ AS1 , which bound EZH2 to enhance H3K27me3 deposition, repressing CDKN1A expression. Discussion Our findings revealed that the YY1 / FOXD2 ‐ AS1 / EZH2 axis drives OSCC progression by epigenetically silencing CDKN1A . FOXD2 ‐ AS1 demonstrates potential as both a prognostic biomarker and therapeutic target, highlighting the need for further exploration of lncRNA ‐based therapeutic approaches in OSCC .