GRIM-19蛋白促进胶质瘤细胞自噬及其机制研究

Glioma is a common type of primary brain tumors, accounting for nearly one-third of all primary brain tumors. Dysregulation of autophagy plays an important role in tumor development and progression, but the effect of autophagy on growth of glioma remains to be illustrated. Our preliminary data had shown that GRIM-19, a mitochondria protein, could promote autophagosome formation in association with a suppression of Akt signaling pathway and an enhancement of CHOP expression in glioma cell lines, indicating that induction of autophagy may be an important pathway for GRIM-19 to achieve its anti-cancer effect. Based on the above mentioned findings, this project aims to explore the effect of GRIM-19-mediated autophagy on growth of glioma cells and its underlying molecular mechanisms by working on clinical glioma samples, glioma cell lines, glioma-transplanted nude mice and GRIM-19 deficient mice. Results yielded by this project are expected to aid in the development of strategies to treat glioma and shed new light on the role of mitochondria in tumor development and progression.

胶质瘤是常见的原发性脑肿瘤，约占原发性脑肿瘤的三分之一。自噬失调在肿瘤发生、发展中具有重要作用，但自噬对胶质瘤细胞生长的影响有待阐明。通过预实验，我们观察到线粒体 GRIM-19蛋白基因的转入增加了胶质瘤细胞自噬小体的数量，同时伴随Akt通路活化的抑制以及CHOP表达的上调，提示该基因可能通过促进自噬而发挥抗肿瘤作用。本项目拟在前期工作的基础上，利用临床胶质瘤病理标本、胶质瘤细胞系、胶质瘤荷瘤裸鼠和GRIM-19缺陷小鼠，研究 GRIM-19促进胶质瘤细胞自噬作用的分子机制以及这一作用对胶质瘤细胞生长的影响。预期所得结果将为胶质瘤的治疗研究提供新的靶点，并加深我们对线粒体在肿瘤发生和发展中作用的理解。

胶质瘤是常见的原发性脑肿瘤，约占原发性脑肿瘤的三分之一。自噬失调在肿瘤发生、发展中具有重要作用，但自噬对胶质瘤细胞生长的影响有待阐明。实验结果表明，在胶质瘤细胞中过表达线粒体基因GRIM-19，增加了胶质瘤细胞自噬小体的数量，同时伴随Akt通路活化的抑制以及CHOP表达的上调，提示该基因可能通过促进自噬而发挥抗肿瘤作用。本项目利用临床胶质瘤病理标本、胶质瘤细胞系、胶质瘤荷瘤裸鼠和GRIM-19缺陷小鼠，研究GRIM-19促进胶质瘤细胞自噬作用的分子机制以及这一作用对胶质瘤细胞生长的影响。研究结果将为胶质瘤的治疗研究提供新的靶点，并加深我们对线粒体在肿瘤发生和发展中作用的理解。