以“Warburg效应”为主要特征的能量代谢重编程在肿瘤进展中起到重要了作用。我们前期研究发现：CPS1在肝癌中低表达并且和临床预后密切相关；CPS1能够影响肝癌细胞的增殖并且具备调控能量代谢重编程的功能；miR-221/222和去乙酰化酶SIRT5在肝癌中异常表达并且协同调控了CPS1的表达和蛋白活性。而目前CPS1在肝癌中的功能及机制尚无相关报道。据此我们推测：miR-221/222和SIRT5协同调控CPS1介导的代谢重编程在肝癌进展中发挥了重要作用。本课题拟基于代谢组学、细胞能量检测和小动物活体成像技术，从组织标本、细胞和动物水平多层次明确CPS1在肝癌进展中的作用；证实CPS1在肝癌中的表达及调控增殖的作用；确定CPS1对肝癌能量代谢重编程的影响；阐明miR-221/222和SIRT5影响CPS1的表达及活性的协同调控机制，以期为肝癌临床治疗及新药研发提供新的理论依据和作用靶点。

Warburg effect plays an important role in tumor progression by energy metabolic reprogramming. Our previous study found that the expression of CPS1 was decreased in HCC, and was closely associated with clinical prognosis. CPS1 could regulate the proliferation of HCC cells, and might possess the ability to influence the energy metabolic reprogramming in HCC cells. Moreover, the expression and activity of CPS1 might be regulated by miR-221/222 and SIRT5 (act as a deacetylase). However, the function of CPS1 in HCC and its mechanism have not been reported. Thus, we speculated that CPS1 regulated by miR-221/222 and SIRT5 might involve in the energy metabolic reprogramming and play an important role in HCC progression. In this study, via clinical tissue specimens, cell experiments and mice tumor-burdened model, we utilized energy metabolism detection system and metabonomics technology systematically to illustrate the function of CPS1 in HCC progression-regulating HCC proliferation by energy metabolic reprogramming. We also explored the upstream regulatory mechanism of CPS1 expression and activity. In a word, we aimed to illustrate the function and mechanism of CPS1 via energy metabolic reprogramming and the regulating mechanism of CPS1 expression and activity by miR-221/222 and SIRT5 in HCC progression. These findings will provide novel ideas and strategies for the targeting treatment of HCC.