Regulatory role of IRF2 in proliferation and invasion of nasopharyngeal carcinoma: Investigation into underlying mechanism.

Abstract

e18052 Background: The recurrence and progression of nasopharyngeal carcinoma (NPC) are major factors contributing to unsatisfactory treatment outcomes. The role of Interferon Regulatory Factor 2 (IRF2) in NPC progression remains unclear. This study aimed to elucidate the biological functions, underlying mechanisms, and clinical significance of IRF2 in NPC. Methods: Subcellular localization and pan-cancer expression profiling of IRF2 were analyzed using the Human Protein Atlas database. Localization and expression levels of IRF2 were assessed in NPC cell lines (CNE1, HONE1, 58F, 6-10B), 64 NPC tissues, 36 chronic nasopharyngitis tissues, and the immortalized nasopharyngeal epithelial cell line NP69 via immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB). Its diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis. Stable IRF2-overexpressing and knockdown NPC cell lines were established. Functional studies were conducted using CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays, as well as a xenograft tumor model in nude mice. The effects of IRF2 on epithelial-mesenchymal transition (EMT) markers and key proteins of the Wnt/β-catenin pathway (GSK-3β, β-catenin) were examined by WB. Nuclear and cytoplasmic fractionation combined with IF was used to observe β-catenin nuclear translocation. Results: IRF2 was significantly upregulated in NPC, primarily localized in the nucleus, and demonstrated diagnostic value (AUC = 0.837, 95% CI: 0.760–0.915). Its expression level positively correlated with T stage and plasma Epstein-Barr virus (EBV) DNA load. IRF2 overexpression promoted NPC cell proliferation, migration, and invasion, while suppressing apoptosis; conversely, IRF2 knockdown produced opposite effects. In vivo experiments confirmed that IRF2 promoted tumor growth. Mechanistically, IRF2 induced EMT (downregulating E-cadherin, upregulating N-cadherin, Snail1, Snail2, ZEB1) and activated the Wnt/β-catenin signaling pathway by upregulating GSK-3β and β-catenin and promoting β-catenin nuclear translocation. Conclusions: IRF2 is primarily located in the nucleus of NPC cells and functions as an oncoprotein, whose expression is associated with local tumor invasion and plasma EBV DNA load. IRF2 drives NPC progression by promoting cell proliferation, migration, invasion, EMT, and inhibiting apoptosis, potentially through activation of the Wnt/β-catenin signaling pathway, suggesting its potential as a therapeutic target.