IRF2-induced Claudin-7 suppresses cell proliferation, invasion and migration of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a common type of malignant tumor worldwide. Claudin-7 (CLDN7) has been reported to exhibit low expression in tissues of patients with OSCC; however, the underlying mechanisms of CLDN7 remain to be elucidated. The present study aimed to investigate the effects of CLDN7 on the progression of OSCC and identify its potential regulatory mechanisms. CLDN7 and interferon regulatory factor-2 (IRF2) expression in several OSCC cell lines were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Following CLDN7 overexpression, cell proliferation, invasion and migration were determined using a Cell Counting Kit-8, colony formation, Transwell and wound healing assays, respectively. The potential binding sites of IRF2 on the CLDN7 promoter were analyzed using the PROMO and JASPAR databases, which were verified via chromatin immunoprecipitation and RT-qPCR assays. The effects of IRF2 and CLDN7 on the biological functions of OSCC cells were examined by transfection with short hairpin RNA (shRNA) against CLDN7 (sh-CLDN7), or IRF2 and CLDN7 overexpression plasmids. The results revealed that CLDN7 and IRF2 expression were significantly downregulated in OSCC cell lines, and CLDN7 overexpression reduced the proliferation, invasion and migration of OSCC cells. Additionally, IRF2 was confirmed to combine with the CLDN7 promoter. CLDN7 silencing reversed the inhibitory effects of IRF2 overexpression on the proliferation, invasion and migration of OSCC cells. Taken together, these findings demonstrated that IRF2-induced CLDN7 upregulation suppressed the proliferation, invasion and migration of OSCC cells, suggesting the possibility of CLDN7 and IRF2 as novel targets for the treatment of OSCC.

Automated summary

This study found that CLDN7 expression is low in OSCC tissues and that overexpression of CLDN7 inhibits the proliferation, invasion, and migration of OSCC cells. IRF2 was found to bind to the CLDN7 promoter and regulate its expression, also affecting the functions of OSCC cells.