A retrospective clinical study of mandibular advancement splint therapy for obstructive sleep apnoea – a 7 year review

Background:Class 3 semaphorins (Sema 3s) are a large group of secreted axon guidance molecules. Increasing studies have shown that Sema3s may act either as tumour suppressor or oncogene in various cancer types. However, little is known in terms of Sema3A in oral squamous cell carcinoma (OSCC). Objectives: To elucidate the role of Sema3A, an axon guiding chemorepulsant in nerve development, in the growth and progression of oral squamous cell carcinoma. Methods: Sema3A was examined in 100 cases of human oral squamous cell carcinoma specimens, 20 cases of normal oral mucosa and cell lines SCC9, CAL27 and HN6 with immunohistochemistry and Western blotting. MTT assay, flow cytometry, cell adhesion and migration, and xenografts were used to evaluate biological significance of Sema3A. Results: Sema3A was significantly reduced in oral squamous cell carcinoma tissues comparing with normal oral mucosa. Overexpression of Sema3A resulted in increased apoptosis, reduced proliferation, adhesion to fibronectin, and migratory capability as well as reduced G2-phase population while increased S-phase population. Cyclin D1, D3 and CDK6 expression were also reduced after Sema3A was over-expressed. In mechanism, we found NF-kb pathway was involved in Sema3A induced growth inhibition and impairment of cancer cell invasion. While transfection of siRNA targeting Sema3A in OSCC cells results in a more progressed growth and invasion as well as elevated NFkb signalling pathway. In addition, in transplanted nude mice, Sema3A overexpression exhibited diminished tumorigenesis and increased apoptisis. Conclusions: Endogenous Sema3A acts as a suppressor of the growth and invasion of human oral squamous cell carcinoma. Acknowledgments: This work is supported in part by the National Natural Science Foundation of China (81402236) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, 2014-37).