应用微阵列芯片研究蛋白质O-GlcNAc糖基化在肿瘤发生中的作用及其机制

项目名称： 应用微阵列芯片研究蛋白质O-GlcNAc糖基化在肿瘤发生中的作用及其机制

项目编号： No.31200604

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 刘英帅

作者单位： 西南大学

项目金额： 23万元

中文摘要： 蛋白O-GlcNAc糖基化修饰是新发现的一种重要的蛋白质翻译后修饰，在细胞生命活动中发挥极其重要的调控作用，近年来日益成为国内外研究的热点。尽管已有研究证明它与肿瘤密切相关，但是目前对O-GlcNAc修饰在肿瘤发生发展中的作用及调控机制知之甚少。本项目结合申请人在蛋白质微阵列芯片领域的研究基础，开发一种快速、灵敏、高特异性和高通量的O-GlcNAc糖基化芯片分析方法，并以不同类型的前列腺癌细胞系为模型，分别研究：O-GlcNAc修饰水平与前列腺癌发生和侵袭的关系；肿瘤相关蛋白的表达及O-GlcNAc糖基化；O-GlcNAc修饰对肿瘤细胞存活、增殖、迁移、凋亡相关信号通路上关键蛋白的表达和磷酸化的影响，以期掌握O-GlcNAc修饰在前列腺癌发生过程中的作用及调控机制。该项目的成功实施不仅可以丰富蛋白质糖基化和肿瘤生物学领域的基础理论，而且为肿瘤的靶向治疗和药物开发提供科学依据。

中文关键词： 蛋白质糖基化；O-连接乙酰葡糖胺修饰；生物芯片；前列腺癌；

英文摘要： Protein O-GlcNAc glycosylation is a new type of post-translational modification of proteins.It plays an essential role in various cellular processes including transcription, stress response, apoptosis, signal transduction, glucose sensing, and proteasomal degradation. It has been demonstrated that O-GlcNAc modification is closely related to some fatal diseases such as cancers. Since the lack of an efficient technology for O-GlcNAc analysis, the role of O-GlcNAc glycosylation in tumor progression is largely unknown till now. Based on the applicant's research experience in protein microarray chip, this project will first develop a powerful platform for a rapid, sensitive, specific, and high-throughput analysis of O-GlcNAc modification. Then,the array biochip-based tecnhonogy will be used to detect the level of O-GlcNAc modification in normal and prostate cancer cells, study the expression and O-GlcNAc glycosylation of tumor-related proteins, and investigate the effect of O-GlcNAc modification on expression and/or phosphorylation of key proteins such as FoxM1, AKT, PI3K, ERK, cyclin D1, Ki67, MMP-2, and MMP-9 in signaling pathways, which are related to cell viability, proliferation, metastasis,and apoptosis.Through above studies, we try to understand the role of O-GlcNAc modification in prostate cancer progression

英文关键词： Protein glycosylation；O-GlcNAc modification；Biochip；Prostate cancer；