铜饥饿诱导自噬介导EZH2降解增强口腔鳞状细胞癌抗肿瘤免疫
Copper starvation induces autophagy-mediated EZH2 degradation to enhance anti-tu-mor immunity in oral squamous cell carcinoma
林晓虎 1赵章 1喻仲麟 1曹巍1
作者信息
- 1. 上海交通大学医学院附属第九人民医院口腔颌面头颈肿瘤科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所(上海市 200001)
- 折叠
摘要
目的:探讨铜饥饿在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的作用,研究SLC31A1在OSCC细胞中的表分子功能和机制.方法:通过沉默SLC31A1塑造铜饥饿环境,CCK-8、细胞划痕和裸鼠皮下成瘤实验评估其对OSCC细胞的影响.沉默SLC31A1后,检测OSCC细胞中自噬及EZH2表达水平的变化.沉默SLC31A1后,乳酸脱氢酶活性检测实验评估其对NK细胞毒性的影响.结果:沉默SLC31A1显著抑制OSCC细胞的增殖、迁移及裸鼠皮下成瘤能力.沉默SLC31A1介导EZH2的降解,增加NK细胞浸润.结论:铜饥饿调节OSCC的增殖、迁移和裸鼠皮下成瘤能力,并通过调控EZH2表达增加NK细胞浸润.
Abstract
Objective:To examined the role of copper starvation in oral squamous cell carcinoma(OSCC),along with the molecular functions and mechanisms of SLC31A1 in these cells.Methods:Initially,SLC31A1 was silenced to induce a copper starvation environment.Sub-sequently,we evaluated the effects of copper starvation on oral squamous cell carcinoma cells using the CCK-8 assay,cell scratch assay,and subcutaneous tumor formation in nude mice.In addition,changes in autophagy and EZH2 expression levels in oral squamous cell carcinoma cells were detected after SLC31A1 silencing.Lactate dehydrogenase activity was assayed to determine its impact on natural killer(NK)cell cytotoxicity after SLC31A1 silencing.Results:Silencing of SLC31A1 significantly inhibited the proliferation,migration,and subcutaneous tu-mor formation ability of oral squamous cell carcinoma cells.Furthermore,silencing SLC31A1 mediated EZH2 degradation and increased NK cell infiltration.Conclusions:Copper starvation can regulate the proliferation,migration,and subcutaneous tumor formation ability of oral squamous cell carcinoma and increase NK cell infiltration by modulating EZH2 expression.
关键词
口腔鳞状细胞癌/铜饥饿/SLC31A1/EZH2/自噬Key words
oral squamous cell carcinoma(OSCC)/copper starvation/SLC31A1/EZH2/autophagy引用本文复制引用
出版年
2024
NETL
NSTL
万方数据