吉林大学学报（医学版）2017，Vol.43Issue(3)：491-495,5.DOI:10.13481/j.1671-587x.20170306
乏氧对人口腔鳞状细胞癌细胞中叉头蛋白P3表达的影响及其机制
Effect of hypoxia on forkhead box P3 expression in human oral squamous cell carcinoma cells and its mechanism
摘要
Abstract
Objective:To investigate the effect of hypoxia on the expression of forkhead box P3 (FOXP3) in human oral squamous cell carcinoma (OSCC) cells,and to clarify its possible epigenetic mechanism.Methods:Two kinds of OSCC cell lines,FaDu and OECM-1,were cultured under normoxic or hypoxic conditions for 18 h.The relative expression levels of FOXP3 mRNA and protein in the cells were detected by Real-time RT-PCR and Western blotting method.The histone modification levels on the FOXP3 gene promoter,including acetylation of histone 3 lysine 4 (H3K4ac),trimethylation of histone 3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3),were analyzed by Chromatin Immunocipitation (ChIP) and quantitative PCR (ChIP-qPCR).The relative expression levels of histone deacetylase 3 (HDAC3) mRNA and inhibitory rates of FOXP3 mRNA expression in the HDAC3-knockdown FaDu cells were investigated by Real-time qPCR and ChIP-qPCR.Results:Compared with normoxic condition,the relative expression levels of FOXP3 mRNA in FaDu and OECM-1 cells under hypoxic condition were decreased by 65.6% and 75.7% (P<0.01).The Western blotting results indicated that compared with normoxic condition,the expression levels of FOXP3 protein in FaDu and OECM-1 cells under hypoxic condition were decreased.The ChIP experiment results showed that compared with normoxic condition,the levels of H3K4ac and H3K4me3 on FOXP3 gene promoter in FaDu cells were decreased under hypoxic condition (P<0.01),while the H3K27me3 level was not changed.In HDAC3-knockdown FaDu cells,compared with control cells,the inhibitory rates of the expressions of H3K4ac and H3K4me3 on FOXP3 gene promoter under hypoxia condition were decreased (P<0.05),so did expressions the FOXP3 mRNA expression (P<0.05).Conclusion:Hypoxia could suppress the expression of FOXP3 by HDAC3-mediated down-regulation of H3K4ac on FOXP3 gene promoter in the human OSCC cells.关键词
乏氧/叉头蛋白P3/口腔肿瘤/癌,鳞状细胞/组蛋白修饰Key words
hypoxia/forkhead box P3/oral neoplasms/carcinoma/squamous cells/histone modification分类
医药卫生引用本文复制引用
闫风琴,范如意,王方正,王磊,叶智敏,傅真富,王建秋..乏氧对人口腔鳞状细胞癌细胞中叉头蛋白P3表达的影响及其机制[J].吉林大学学报（医学版）,2017,43(3):491-495,5.基金项目
国家自然科学基金资助课题(81301850) （81301850）
浙江省教育厅科研项目资助课题(Y201328812) （Y201328812）
