棕榈酰转移酶ZDHHC17在脑胶质瘤发生发展中的作用机制研究

ZDHHC蛋白家族被报道与多种恶性肿瘤病发相关联。由ZDHHC蛋白介导的棕榈酰化是神经系统中蛋白修饰的关键信号，而其在脑胶质瘤发生发展中的作用尚未阐明。前期研究发现，在胶质瘤组织中，棕榈酰转移酶ZDHHC17有着高丰度的表达，并且与胶质瘤患者术后不良有着明显的相关性。敲低ZDHHC17表达，胶质瘤侵袭增殖等恶性表型受到明显抑制。本项目在既往研究基础上，将从胶质瘤分子亚型和细胞异质性等研究角度出发，以探究ZDHHC17在胶质瘤恶性发生发展中的作用机制为主线，利用免疫组化、酰基-生物素交换法、流式细胞术和裸鼠移植瘤等技术，明确ZDHHC17表达与患者分子病理学特征的关联性，阐明ZDHHC17介导预后不良的调控模式，建立转录因子、信号传导以及蛋白翻译后修饰在胶质瘤恶性化进展过程中的分子互作网络，并尝试获得靶向ZDHHC17蛋白的抗肿瘤药物。

The ZDHHC protein family has been reported to be associated with the occurrence of some malignant tumors. Protein palmitoylation mediated by ZDHHC family play important roles in neural development, but the role of ZDHHC family in the development and progression of glioma is not known. In glioma tissues, ZDHHC17 was expressed at a high abundance, and was significantly associated with poor prognosis in patients with glioma. Knockdown of ZDHHC17, the invasion and proliferation of glioma cells was significantly inhibited. Based on the preliminary results, we design our project to clarify the regulatory mechanism of ZDHHC17 in the biological characteristics of glioma cells, to establish the molecular network with posttranslational modification of proteins, signaling transduction and transcription factors on glioma malignant development and progression, and to achieve a novel type of anti-cancer inhibitors targeting ZDHHC17.