肝癌的诊断和治疗仍然是当今医学的重大难题。因此，发现肝癌的早期诊断标志物和有效的治疗靶点是一项亟待解决的任务。研究发现，去泛素化酶（DUB）可以通过介导癌蛋白的去泛素化和稳定，促进某些肿瘤的细胞增殖、侵袭转移以及药物抵抗，因而成为一类肿瘤治疗的新靶点。然而，DUB在肝癌发生发展中的作用及其调控机制尚不清楚。我们前期研究发现，去泛素化酶USP1在肝癌中呈现高表达，与肝癌患者的生存预后呈负相关。并且，USP1可以促进肝癌细胞的生长和侵袭转移，表明USP1在肝癌的发生发展中发挥关键作用。更重要的是，USP1与其相关因子UAF1结合，介导核糖体蛋白RPS16的去泛素化，从而提升RPS16的蛋白水平。因此，我们提出科学假说：USP1-UAF1复合体可能通过调控RPS16泛素化降解促进肝癌的恶性进展。本研究旨在从分子细胞生物学、动物水平以及临床大数据分析解决这一科学问题，为肝癌的诊断和治疗提供新策略。

The diagnosis and treatment of hepatocarcinoma still challenge current medicine. Therefore, identifying novel biomarkers and effective therapeutic targets for early diagnosis and treatment of hepatocarcinoma are urgently needed. Studies have unraveled that deubiquitinases (DUBs) promote cell proliferation, invasion and metastasis, and therapeutic resistance via mediating deubiquitination and stabilization of oncoproteins in several certain cancers, which renders them became a class of novel targets for cancer treatment. However, roles of DUBs in the occurrence and development of hepatocarcinoma and their regulatory mechanisms remain poorly understood. Our preliminary explorations showed that the expression of USP1 is remarkably upregulated in hepatocarcinoma and negatively correlated with overall survival of patients with hepatocarcinoma. Further investigations showed that USP1 promotes the growth and metastasis of hepatoma cells, indicating that USP1 plays a critical role in the occurrence and development of hepatocarcinoma. Moreover, we revealed that USP1 functions with the binding of its co-activator named UAF1. The USP1-UAF1 complex mediates deubiquitination and stabilization of ribosomal protein RPS16, and thereby elevating the protein level of RPS16. Therefore, we raise a scientific hypothesis that the USP1-UAF1 complex facilitates malignant progression of hepatocarcinoma possibly via modulating RPS16 ubiquitination and degradation. This study aims to prove the scientific hypothesis for providing novel strategies for hepatocarcinoma diagnosis and treatment by numerous experiments at levels of molecular and cellular biology, animal models and clinically massive data analysis.