核仁与肿瘤发生有着密切联系，近期研究发现核仁中核糖体生成过度活化会促进肿瘤的发生发展，但核仁在肝癌发生中的作用还不清晰。核仁蛋白Bms1和Rcl1最初在酵母中发现，二者形成复合物在核糖体生成中发挥关键功能。我们前期发现人和斑马鱼的Bms1和Rcl1也能够形成复合物，且斑马鱼Bms1和Rcl1失活导致肝脏发育受阻，以及抑癌基因p53在bms1突变体的核仁中被激活。通过生信分析肝癌样本的基因表达显示Bms1和Rcl1的表达水平分别呈上升和下降趋势，且显著影响患者的生存率。综合前期的研究结果，我们推测Bms1和Rcl1可能在肝癌的发生发展过程中具有重要作用。本项目将结合临床肝癌样本、斑马鱼突变体和HCC模型，深入研究核仁蛋白Bms1和Rcl1的互作特性以及在肝癌发生中的作用机制。研究结果将进一步拓宽核仁的生物学功能，并为肝癌的治疗提供新的思路和理论基础。

There is a close connection between nucleolus and tumorigenesis. Recent study showed that the over-activation of ribosome biogenesis, which take place in the nucleolus, could promote the development and progression of tumor. However, the function of nucleolus in hepatocarcinogenesis is not clear. The nucleolar protein Bms1 and Rcl1 are firstly identified in yeast and play essential roles in ribosome biogenesis by forming complex. Previously, we reported that Bms1 and Rcl1 in human and zebrafish can also form complex, and loss-of-function of Bms1 and Rcl1 in zebrafish led to the arrest of liver development and the tumor suppressor p53 was activated in nucleolus in bms1 mutant zebrafish. Analysis of gene expression in liver cancer samples through bioinformatics showed that the expression level of Bms1 and Rcl1 was up- and down-regulated, respectively, which had a significant impact on the survival of patients. Based on these results, we speculate that nucleolar protein Bms1 and Rcl1 may play an important role in the development and progression of liver cancer. This project will investigate the interaction fashion and molecular mechanism of Bms1 and Rcl1 in hepatocarcinogenesis by utilizing clinical sample of liver cancer, gene mutation and HCC model of zebrafish. The results will further broaden the biological function of nucleolus and provide new ideas and theoretical basis for the treatment of liver cancer.