基于人工杂合高亲和泛素结合蛋白的肝癌转移复发蛋白质泛素化失调分子机制的定量泛素化蛋白质组研究

肝癌在我国发病率高，危害大。肝癌后期的转移复发是影响肝癌预后和疗效的主要因素，其机制亟待研究。泛素是真核生物体内广泛存在的蛋白质性质的信号分子。蛋白质泛素化引导着蛋白质降解、细胞内定位、转运、DNA修复、酶活力调控等几乎所有的生物学功能，并与肝癌的发生、发展和转移复发关系密切，但尚无泛素化蛋白质组学的研究报道。本申请依托申请人团队新近发展的高效无偏性人工杂合泛素结合蛋白ThUBD及其配套的泛素化蛋白富集技术，建立大规模泛素化蛋白质组高效研究技术体系，系统定量比较中国人遗传背景的系列转移潜能逐步增加的肝癌细胞系MHCC97L、MHCC97H和HCCLM6的泛素化蛋白质组，建立人肝癌相关泛素化蛋白质及其修饰位点数据库，鉴定并验证肝癌转移相关的泛素化失调蛋白，阐明其累及的修饰位点及其信号通路，揭示肝癌转移调控泛素化相关的分子机制，为肝癌预后和个性性诊治提供数据支持。

Hepatocellular carcinoma (HCC) is one of the most commonly present human malignancies worldwide. Metastasis and relapse of HCC hinder the therapeutic effect severely, but we know little about the underlying mechanisms. Ubiquitin is a small protein-like signaling molecule. Ubiquitination is one of the most common post-translational modifications, regulating protein degradation, localization, transportation, DNA repair, and enzymatic activity. It has been known that ubiquitination is closely related with the development, progression and metastasis of HCC. As for our knowledge, there is no ubiquitome study in this field. In this application, based on the state-of-the-art ubiquitome technology recently developed in our lab, we will systematically investigate the ubiquitome of MHCC97L, MHCC97H and HCCLM6 cells originated stepwisely from one Chinese HCC patient. We can construct a HCC related ubiquitome database, identify and elucidate the molecular mechanisms of dysfunctional ubiquitylated proteins involved in metastasis of HCC to support precision medicine of HCC in the near future.