Role of cadherin gene dysregulation in WNT signaling and nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignancy associated with genetic alterations and tumor progression. Cadherin genes (CDH1, CDH2, and CDH3) play key roles in cell adhesion, migration, and tissue integrity, and their role in NPC remains underexplored. This study investigates the expression, mutation patterns, and prognostic significance of cadherin genes in NPC. Eight normal nasal cell lines and six NPC cell lines were cultured. Gene expression was analyzed using RT-qPCR and validated using GSCA and HPA databases. Promoter methylation, mutation, and CNV analyses were conducted using OncoDB and cBioPortal. Gene knockdown experiments were performed in 5-8 F NPC cells using siRNA targeting CDH1, CDH2, and CDH3, followed by cell proliferation, colony formation, and wound healing assays. CDH1, CDH2, and CDH3 were significantly upregulated in NPC cell lines, and high expression correlated with poor prognosis. Mutational analysis revealed mutations in 100% of HNSC or NPC samples, with CDH3 showing the highest mutation rate (44%). CNV analysis showed amplifications in cadherin gene regions. Knockdown of cadherin genes in 5-8 F and C666-1 cells significantly reduced cell proliferation, colony formation, and migration. Additionally, Cadherin gene knockdown upregulated AXIN1 and WNT3A, indicating involvement in the WNT signaling pathway. Cadherin genes are upregulated in NPC, associated with poor prognosis, and regulate key cancer-related processes. They represent potential diagnostic, prognostic, and therapeutic targets for NPC.