自噬在PDGFA/PDGFB差异性调控PDGFRA的机制研究及对胶质母细胞瘤的影响

人胶质母细胞瘤是星形细胞肿瘤中恶性程度最高的胶质瘤，严重危害人类健康，而自噬在其中发挥着重要的作用。本课题组研究发现自噬显著影响介导Proneural类胶质母细胞瘤主要特征的关键分子——PDGFRA的表达，且这种作用在PDGFA/PDGFRA和PDGFB/PDGFRA两条通路中具有明显差异，本项目拟在此研究基础上，通过蛋白结合组学分析PDGFRA受PDGFA/PDGFB刺激后下游结合蛋白复合物，筛选PDGFRA调控的关键乙酰化调控蛋白，揭示乙酰化调控蛋白对自噬状态的影响以及影响的自噬相关靶点，确定自噬对PDGFRA下游结合蛋白复合物、信号转导以及最终对胶质母细胞瘤细胞生长和侵袭的影响。本研究首次探讨了PDGFRA受PDGFA以及PDGFB差异性调控及其与自噬的相互作用，为揭示胶质母细胞瘤治疗预后的新药物和新的诊治策略提供理论基础。

Human glioblastoma is the most malignant glioma in astrocytic tumors, which seriously harms human health, and autophagy plays an important role in it. Our group found that autophagy significantly influences the expression of PDGFRA, a key molecule that mediates the main features of proneural-like glioblastoma, and this effect is significantly different in PDGFA/PDGFRA and PDGFB/PDGFRA pathways. In this project, based on this study, the downstream binding protein complexes of PDGFRA stimulated by PDGFRA/PDGFB were analyzed, and the key acetylated regulatory proteins regulated by PDGFRA were screened to reveal the effect of acetylated regulatory proteins on autophagy status and autophagy related genes. The effects of autophagy on PDGFRA downstream binding protein complexes, signal transduction, and eventual glioblastoma cell growth and invasion were determined. This study first investigated the differential regulation of PDGFRA and PDGFB by PDGFRA and its interaction with autophagy, providing a theoretical basis for the discovery of new drugs and new strategies for the diagnosis and treatment of glioblastoma.