The Role Of Sigma-1 Receptor Expression In The Biological Behavior Of Oral Squamous Cell Carcinoma

Objective Oral cancer is recognized as a common malignant tumor in the head and neck region,ranking the top in the global cancer incidence ranking.Because most malignant tumors in the oral and maxillofacial region are derived from epithelial tissue,oral squamous cell carcinoma(OSCC)is the most common one.Due to the particularity of its location,OSCC often occurs regional lymph node metastasis,especially in the late stage,which is prone to recurrence and distant metastasis and has a poor prognosis.Although there are more and more researches on the clinical and molecular mechanisms of OSCC,the exact specific recognition molecules have not been found yet,and advanced metastasis is still a thorny problem that threatens the life and health of patients.Therefore,the exploration and identification of new diagnostic and therapeutic molecules,so as to achieve early detection and treatment of OSCC,and improve the prognosis remains the main task of current OSCC research.Recent studies have found that the sigma-1 receptor,as a chaperone protein,is closely related to various tumors.Studies have shown that the sigma-1 receptor is up-regulated in a variety of human cancer cells and tissues,and is involved in the regulation of the biological behavior of tumor cells.However,the expression of sigma-1 receptor in OSCC and its effect on the biological behavior of OSCC remain unclear.In addition,previous studies have proved that sigma-1 receptor plays an important role in cancer cells by regulating the mechanism related to ion channels,and may affect the occurrence and development of cancer by interacting with voltage-gated sodium channels(VGSC)Nav1.5,but the specific mechanism of action has not been determined.Based on the above studies,we detected the expression level of sigma-1 receptor in OSCC tissues and cell lines,and transfected with specific siRNA to reduce the expression of sigma-1 receptor in OSCC cells,so as to investigate the role of sigma-1 receptor in the proliferation,migration and invasion of OSCC cells.In addition,we also examined the effect of transfection on the expression level of Nav1.5,and preliminarily explored the possible interaction between sigma-1 receptor and Nav1.5.Methods Immunohistochemical method was used to detect the difference in the expression of sigma-1 receptor between human OSCC tissues and adjacent normal tissues.Western blotting and immunofluorescence were used to detect the protein expression and location of sigma-1 receptor in human OSCC cell lines.GEPIA(Gene Expression Profiling Interactive Analysis)database was used to analyze the correlation between sigma-1 receptor expression level and prognosis of patients with OSCC.The expression of sigma-1 receptor was down-regulated by transfection specific siRNA.The proliferation,migration and invasion of OSCC cells after transfection were detected by CCK-8 and Transwell assay.The effect of down-regulation of sigma-1 receptor expression on the expression level of Nav1.5 in OSCC cells was detected by q RT-PCR and Western blotting.The experimental results were collated and statistically analyzed,P<0.05 indicates a statistically significant difference.Results Immunohistochemical analysis showed that the expression of sigma-1 receptor was higher in OSCC tissues than in normal tissues.Western blotting showed that the sigma-1 receptor was expressed in all the four OSCC cell lines,and the highest expression level was found in Cal-27 cells,which was selected for the subsequent experiments.The results of GEPIA database analysis showed that the expression level of SIGMA-1 receptor was negatively correlated with overall survival in patients with OSCC.Immunofluorescence and confocal microscopy showed that the sigma-1 receptor was distributed throughout the cytoplasm of CAL-27 cells,but mainly in the plasma membrane region.CCK-8 analysis showed that the downregulated expression of sigma-1 receptor reduced the proliferation of CAL-27 cells through its specific siRNA.Transwell analysis showed that reducing the expression of sigma-1 receptor could significantly inhibit the migration and invasion of CAL-27 cells.In addition,we found that down-regulation of sigma-1 receptor expression resulted in decreased protein and mRNA expression levels of voltage-gated sodium channel Nav1.5.Conclusions Sigma-1 receptor participates in the occurrence and development of OSCC,promotes the proliferation,migration and invasion of OSCC cells,and may be involved in the progression of OSCC by regulating the Nav1.5 ion channel.