O-GlcNAc糖基化修饰对不同恶性级别脑胶质瘤侵袭及增殖能力影响的研究

Glioma is the most common primary tumor of the central nervous system, with the characteristics of invasive growth and poor prognosis, and the traditional treatments often fail to achieve satisfactory results. O-GlcNAcylation is a dynamic and reversible protein posttranslational modification that exists on serine / threonine residues, which is closely related to the development of tumor tissue. In view of the highly aggressive and rapidly proliferating characteristics of glioma, this project aims to screen out the core protein that can affect the invasion and proliferation of glioma by comparing the differential expression of protein O-GlcNAcylation in different grades of malignant glioma; to verify the correlation between the core protein O-GlcNAcylation and the malignant degree of glioma using clinical specimens; to analyze the effects of glycosylation in changing the core protein stability by molecular biology means. The purpose of this project is to elucidate the new mechanism of O-GlcNAcylation affecting the occurrence of glioma and to provide new ideas and theoretical guidance for its diagnosis and treatment.

脑胶质瘤是中枢神经系统最常见的原发性肿瘤，具有浸润性生长、预后差的特点，传统治疗往往无法取得满意疗效。O-GlcNAc糖基化是存在于蛋白质丝/苏氨酸残基上的动态、可逆的蛋白质翻译后修饰，与肿瘤组织发展密切相关。针对脑胶质瘤高度侵袭性和高速增殖的特性，本项目拟通过对比不同恶性程度脑胶质瘤中蛋白O-GlcNAc糖基化的差异性表达，筛选出能够影响脑胶质瘤侵袭和增殖的核心蛋白；利用临床病例标本验证核心蛋白O-GlcNAc糖基化修饰与脑胶质瘤恶性程度的相关性；通过分子生物学手段分析糖基化对核心蛋白稳定性变化的影响。本项目旨在阐明O-GlcNAc糖基化影响脑胶质瘤发生的新机制，为其诊断和治疗提供新的思路和理论指导。

脑胶质瘤是中枢神经系统最常见的原发性肿瘤，具有浸润性生长、预后差的特点，传统治疗往往无法取得满意疗效。O-GlcNAc糖基化是存在于蛋白质丝/苏氨酸残基上的动态、可逆的蛋白质翻译后修饰，与肿瘤组织发展密切相关。针对脑胶质瘤高度侵袭性和高速增殖的特性，本项目发现神经干细胞条件培养基对脑胶质瘤具有抑制作用，通过分析其对不同恶性程度脑胶质瘤肿瘤生物特性的改变，以及O-GlcNAc糖基化水平的变化，分析并筛选出抑制脑胶质瘤侵袭和增殖的核心蛋白及信号通路；利用临床病例标本验证核心蛋白O-GlcNAc糖基化修饰与脑胶质瘤恶性程度的相关性。本项目旨在阐明O-GlcNAc糖基化影响脑胶质瘤发生的新机制，为其诊断和治疗提供新的思路和理论指导。