Tight junction protein CLDN17 serves as a tumor suppressor to reduce the invasion and migration of oral cancer cells by inhibiting epithelial-mesenchymal transition

Abstract

ObjectiveTo investigate claudin-17 (CLDN17) expression in oral cancer and its effect on epithelial-mesenchymal transition (EMT), invasion and migration in oral cancer cells. MethodsThe GEO2R tool was used to analyze gene expression in two microarray datasets (GSE74530 and GSE146483) derived from the Gene Expression Omnibus (GEO) database. Gene Expression Profiling Interactive Analysis (GEPIA) verified CLDN17 expression in head and neck squamous cell carcinoma (HNSC) patients. Moreover, oral cancer cells were transfected with CLDN17 overexpression plasmid or CLDN17 shRNA to evaluate cell invasion and migration. Gene and protein expression was detected by qRT–PCR, immunohistochemistry and western blotting. ResultsCLDN17 was one of the top 200 differentially expressed genes in the GSE74530 and GSE146483 datasets and was downregulated in oral cancer. CLDN17 expression was higher in HNSC tissues, and it was related to TNM staging. In HNSC tumors, CLDN17 expression was positively correlated with CDH1 but negatively related to VIM, SNAIL1, SNAIL2, and TWIST1. Meanwhile, we found that CLDN17 expression was lower in oral cancer tissues; it declined with higher T status, N status, M status and staging, lower differentiation grade, and a worse prognosis. Upregulation of CLDN17 inhibited the invasion and migration of oral cancer cells, with elevated CDH1 and reduced VIM, SNAIL1, SNAIL2, and TWIST1, while CLDN17 downregulation had the opposite effects. ConclusionCLDN17 may serve as a tumor suppressor in oral cancer since it could reduce the invasion and migration of cells by inhibiting the EMT process, thus becoming a potential therapeutic target in oral cancer.