GGA1和自噬囊泡在前列腺癌发生中的作用及机制研究

Autophagy is a conservative bulk degradation mechanism in all eukaryotic cells. Autophagy is reported be closely related to tumorigenesis. However, the role of Autophagic vesicles formation and transport in tumorigenesis is still unclear. Our previous study found that triptolide could induce autophagy in prostate cancer cells, and found a target protein-GGA1, as a autophagic vesicles related gene, GGA1 is overexpressed in prostate cancer (PCa), along with abnormally elevated autophagy level, but the function of triptolide and GGA1 interaction in autophagy regulation and PCa progression is unknown. Therefore, this project is intended to reveal the relationship between Autophagic vesicles and PCa, inquiry the role of GGA1 in autophagy regulation and PCa progression, and study the role of autophagy vesicles in triptolide induced PCa cell death. The project will help to reveal the relationship between autophagy vesicles and PCa progression, assess the feasibility of targeting autophagy vesicles related gene in PCa treatment, which will lay a foundation for uncovering the mechanism of PCa and developing new anti-PCa therapeutic strategies.

自噬是真核细胞中的一种批量降解机制。自噬与肿瘤发生密切相关，但自噬囊泡的形成、转运在肿瘤中的作用和机制还不清楚。我们的前期研究发现一种中药来源的活性小分子化合物—雷公藤甲素能够诱导前列腺癌细胞发生自噬，并筛选到一个靶蛋白—GGA1，GGA1作为自噬囊泡相关基因，其过表达伴随着自噬水平的异常升高，但这种互作在自噬调控和前列腺癌中的功能还不清楚。因此，本项目拟以前列腺癌为研究对象，揭示自噬囊泡的形成、转运与前列腺癌之间的关系；研究GGA1过表达在前列腺癌发生发展和自噬异常中的作用和机制；探究GGA1在自噬囊泡形成、转运中的作用；并利用雷公藤甲素探索靶向自噬囊泡基因在前列腺癌治疗中的意义。本项目的开展将有助于揭示GGA1，自噬囊泡形成、转运与前列腺癌发生发展的相互关系及其机制，评估靶向自噬囊泡相关基因在前列腺癌治疗中的价值，为阐明前列腺癌病理转化机制和开发新的治疗策略提供实验基础及理论依据。