The Competitive Mechanism Of Ezh1 And Ezh2 In Promoting Oscc

To elucidate the roles and competitive interplay of Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2) in promoting oral squamous cell carcinoma (OSCC) progression. Bioinformatics analysis was performed using data from the Cancer Somatic Mutation Database (COSMIC) and The Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) compared EZH1/EZH2 protein levels in OSCC (N=63) and normal oral tissues. Lentiviral vectors were used to establish EZH1/2-overexpressing OSCC cell lines. Functional assays evaluated proliferation, clonogenicity, stemness, and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation (Co-IP) assessed competitive binding of EZH1/EZH2 to Polycomb Repressive Complex 2 (PRC2). COSMIC data indicated rare EZH1/2 mutations in head and neck squamous cell carcinoma (HNSCC). TCGA and IHC revealed EZH2 upregulation and EZH1 downregulation in OSCC. RNA-seq analysis demonstrated that EZH2 overexpression correlated positively with epithelial proliferation, stemness, EMT, and migration, while EZH1 showed inverse trends. Functional assays confirmed that EZH2 upregulated Ki67, Cyclin A2, SOX2, BMI1, N-CAD, Vimentin, and Snail, downregulated E-CAD, and enhanced clonogenicity, proliferation, spheroid formation, ALDH^bright+ stem cells, and invasion. Conversely, EZH1 overexpression suppressed these effects. Mechanistically, EZH2 elevated H3K27me2/3 levels and competitively bound PRC2, displacing EZH1. EZH1 and EZH2 exert opposing roles in OSCC progression. EZH2 promotes oncogenesis by enhancing stemness, EMT, and proliferation via PRC2-mediated H3K27 methylation, while EZH1 antagonizes these effects. Their competitive interaction with PRC2 highlights a novel regulatory axis in OSCC.