FOXA1 Transcriptional Repression of PLSCR1 Inhibits Tongue Squamous Cell Carcinoma Progression.

Tongue squamous cell carcinoma (TSCC) is a major subtype of head and neck cancer with limited treatment regimens. This paper examined phospholipid scramblase 1 (PLSCR1) and forkhead box protein A1 (FOXA1) expression patterns and function in TSCC progression. Abnormally high expression of PLSCR1 was screened by the GEO datasets, and PLSCR1 expression in TSCC cells was verified. The upstream mechanism of abnormally elevated PLSCR1 was investigated by bioinformatics analysis, and FOXA1 expression in TSCC cells was detected. The interaction between FOXA1 and the PLSCR1 promoter in cells was detected by chromatin immunoprecipitation and dual-luciferase assay. The TSCC cell malignant phenotype was examined after different lentiviral vector treatments. Xenograft tumors were induced in mice to verify the mechanism. PLSCR1 was highly expressed in TSCC, while FOXA1 was downregulated. PLSCR1 knockdown inhibited TSCC cell proliferation, migration, and invasion, and upregulated apoptosis. Ectopic expression of FOXA1 repressed the malignant behaviors of TSCC cells. FOXA1 was enriched in the PLSCR1 promoter in TSCC cells, and FOXA1 transcriptionally inhibited PLSCR1 expression. In rescue experiments, overexpression of FOXA1 inhibited TSCC progression, and this could be reversed by overexpression of PLSCR1. Overall, FOXA1 prevents TSCC progression through transcriptional repression of PLSCR1.