组蛋白乳酸化修饰在头颈肿瘤中的表达及意义
Expression and significance of histone lactylation modifications in head and neck tumors
王睿捷 1马海龙 1张志愿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 200011
- 折叠
摘要
目的:观察组蛋白乳酸化修饰在头颈肿瘤中的表达水平及乳酸对肿瘤细胞增殖能力的影响.方法:应用多色免疫荧光组织芯片检测69例头颈肿瘤组织中泛乳酸化(PKLa)和组蛋白H3K9乳酸化(H3K9La)的修饰水平,分析其与患者临床特征的关系.在头颈肿瘤细胞受到乳酸刺激后,使用蛋白免疫印迹技术检测PKLa、H3K9La的修饰水平改变.采用SPSS 17.0软件包对数据进行统计学分析.结果:头颈肿瘤组织中PKLa修饰水平显著高于正常黏膜组织.临床样本分析表明PKLa修饰水平与年龄、TNM分期显著相关(P＜0.05),而与性别、颈淋巴结转移、病理分化无相关性(P＞0.05).蛋白免疫印迹结果证明,组蛋白是头颈肿瘤细胞乳酸化主要的响应蛋白,乳酸刺激能够提高头颈肿瘤细胞增殖能力,进一步确定头颈肿瘤细胞中H3K9La修饰具有乳酸依赖上调.免疫荧光染色证明,头颈肿瘤组织H3K9La水平较高.结论:头颈肿瘤患者中具有较高的组蛋白乳酸化修饰水平,与头颈肿瘤进展有潜在关系.
Abstract
PURPOSE:To observe the expression level of histone lactylation modification in head and neck tumors and the effect of lactic acid on the proliferative ability of tumor cells.METHODS:Multicolor immunofluorescence was applied to detect the modification levels of PKLa and histone H3K9 lactylation(H3K9La)in 69 head and neck tumor tissues with tissue microarrays,and analyze their relationship with the clinical characteristics of the patients.Changes in the modifica-tion levels of PKLa,and H3K9La were detected by protein immunoblotting technology after head and neck tumor cells were stimulated by lactic acid.SPSS 17.0 software package was used for data analysis.RESULTS:PKLa modification levels were significantly higher in head and neck tumor tissues than in normal mucosal tissues.Analysis of clinical sam-ples revealed that PKLa modification levels were significantly correlated with age and TNM stage(P＜0.05),but not with gender,cervical lymph node metastasis,or pathological differentiation(P＞0.05).Protein immunoblotting results demonstrat-ed that histones were the main response proteins for lactylation modification in head and neck tumor cells,while lactic acid stimulation was able to increase the proliferation capacity of head and neck tumor cells.It was further determined that H3K9La modification in head and neck tumor cells had lactate-dependent up-regulation.Immunofluorescence staining al-so demonstrated higher levels of H3K9La in head and neck tumor tissues.CONCLUSIONS:Higher levels of histone lactate modification in head and neck tumor patients are potentially associated with head and neck tumor progression.
关键词
头颈肿瘤/乳酸化修饰/表观遗传学/翻译后修饰Key words
Head and neck tumors/Lactylation modification/Epigenetics/Post-translational modification引用本文复制引用
出版年
2024
NETL
NSTL
万方数据