Voltage-gated Potassium Channel Subtype Kv3.4 Is Involved In The Proliferation And Invasion Of Oral Squamous Cell Carcinoma

Objective Oral squamous cell carcinoma(OSCC)is one of the most common malignant tumors in oral tumors in China,often has regional lymph nodes and distant metastases.In view of the difficulty in the treatment and the high mortality rate of oral squamous cell carcinoma,more and more scholars have focused on molecular targeted therapy.At present,molecular targeted therapy has gradually become a vital part of OSCC comprehensive sequence therapy,and seeking more precise and effective molecular targets has become the key to OSCC treatment.A number of studies have shown that voltage-gated potassium channels are closely related to a variety of cancers including oral squamous cell carcinoma.The relationship between voltage-gated potassium channel subtype Kv3.4 and tumors is a hot topic.This study aimed to investigate the expression of Kv3.4 in oral squamous cell carcinoma,and association between Kv3.4 and proliferation,invasion and apoptosis of oral squamous cell carcinoma cells.This study aimed to verify the association between Kv3.4 and the development of oral squamous cell carcinoma,and to explore its mechanism of action.This research provided new targets for the prevention and treatment of oral squamous cell carcinoma.Method The oral squamous cell carcinoma cell line SCC3 was cultured,and the expression of Kv3.4 in SCC3 cells was confirmed using laser confocal microscopy.We used liposome-transfected small interfering RNA(siRNA-KCNC4)to knock out KCNC4 gene expressing Kv3.4 in OSCC cell line SCC3,and verified changes in mRNA and protein expression levels of Kv3.4 using qRT-PCR and Western Blot.Changes in proliferation and invasion ability of SCC3 cells after transfection were detected using CCK-8 and Transwell.Flow cytometry was used to detect apoptosis and cell cycle changes after transfection.Western Blot was used to detect changes in the expression levels of cyclin and invasion-related proteins.Statistical analysis was performed on the experimental data.Analysis of two groups of data used student's t-test.Analysis of more than two groups of data used one-way ANOVA.Result Immunocytochemistry showed that Kv3.4 was widely expressed on the cytoplasm and cell membrane of SCC3 cells.After transfection of siRNA-KCNC4,with the decrease of Kv3.4 expression level,the proliferation ability of SCC3 cells decreased(P<0.001),the invasive ability decreased(P<0.001),and apoptosis increased(P<0.001),indicating Kv3.4 may be involved in the development of oral squamous cell carcinoma.The results also showed that the expression of cyclin D1,cyclin E1 and matrix metalloproteinase-9(MMP-9)was significantly decreased after KCNC4 gene knockout,and the cell cycle G0 / G1 was arrested.This represents the regulation of Kv3.4 on oral squamous cell carcinoma,possibly through cyclin and matrix metalloproteinases.Conclusion Kv3.4 can affect the biological behavior of oral squamous cell carcinoma by regulating cell cycle and regulating the expression of MMPs.It is speculated that Kv3.4 may be an important target in the regulation network of invasion,proliferation and apoptosis of oral squamous cell carcinoma,and it has further research value.