HIF-1α Regulates Proliferation and Invasion of Oral Cancer Cells through Kv3.4 Channel

This study aims to explore the regulatory mechanism of hypoxia-inducible factor HIF-1 alpha on Kv3.4. Oral squamous cell carcinoma (OSCC) cell lines SCC3 and CAL27 were used in this study. Western blotting and qRT-PCR methods were used to detect Kv3.4 expression levels in OSCC and their adjacent tissues. The expression changes of Kv3.4 and HIF-1 alpha in a hypoxic environment were detected in cell lines. The stable OSCC cell lines with knockouts of HIF-1 alpha and Kv3.4 were constructed. Transwell and CCK-8 assays were used to detect changes in the invasion, migration and proliferation ability after transfection. Chromatin immunoprecipitation and luciferase reporter gene assays were used to determine the regulatory and binding sites of HIF-1 alpha on Kv3.4. The expression level of Kv3.4 in oral cancer tissue was higher than normal oral epithelium's regular value. The expression level of HIF-1 alpha and Kv3.4 increased under hypoxia. Knocking out HIF-1 alpha and Kv3.4 could reduce the invasion, migration and proliferation of cells. A down regulation of HIF-1 alpha will reduce the Kv3.4 expression level. Overexpressing Kv3.4 after knocking down HIF-1 alpha partially restored the proliferation and invasion of cell lines. Therefore, HIF-1 alpha regulates the invasion, migration and proliferation of oral cancer cells by regulating Kv3.4 expression.