Wang Jinxin, Zhang Cong, Wang Junrong, Wang Lei, Liu Li, Duan Chunbin
Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.
Cell Biochem Biophys. 2025 May 30. doi: 10.1007/s12013-025-01785-4.
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.
舌鳞状细胞癌（TSCC）是头颈癌的一种主要亚型，治疗方案有限。本文研究了磷脂翻转酶1（PLSCR1）和叉头框蛋白A1（FOXA1）在TSCC进展中的表达模式和功能。通过GEO数据集筛选出PLSCR1的异常高表达，并验证了TSCC细胞中PLSCR1的表达。通过生物信息学分析研究了PLSCR1异常升高的上游机制，并检测了TSCC细胞中FOXA1的表达。通过染色质免疫沉淀和双荧光素酶测定检测细胞中FOXA1与PLSCR1启动子之间的相互作用。在不同的慢病毒载体处理后检测TSCC细胞的恶性表型。在小鼠中诱导异种移植肿瘤以验证该机制。PLSCR1在TSCC中高表达，而FOXA1下调。敲低PLSCR1可抑制TSCC细胞的增殖、迁移和侵袭，并上调细胞凋亡。异位表达FOXA1可抑制TSCC细胞的恶性行为。FOXA1在TSCC细胞的PLSCR1启动子中富集，并且FOXA1转录抑制PLSCR1的表达。在挽救实验中，FOXA1的过表达抑制了TSCC的进展，而PLSCR1的过表达可逆转这种抑制作用。总体而言，FOXA1通过转录抑制PLSCR1来阻止TSCC的进展。
