肝癌是全球第三大与癌症相关的死亡原因，其发病隐匿、疾病进展快、预后不乐观，严重威胁人类健康，缺乏有效治疗方法。维持DNA复制叉稳定性和对复制压力造成的损伤进行修复是肝癌发生的重要调控机制，然而尚未找到其中的关键因子。聚（ADP-核糖）水解酶（PARG）是参与DNA复制和损伤修复的蛋白酶，在多种肿瘤中异常高表达，但PARG在肝癌中的功能及调控机制目前尚无报道。我们的前期结果显示，PARG在肝癌患者中高表达，且抑制PARG能够使肝癌细胞阻滞在S期，抑制肝癌细胞DNA复制。本项目拟探讨PARG在肝癌中的生物学功能及机制：（1）PARG在DNA复制中的作用及其在肝癌细胞中的功能；（2）明确PARG调控的DNA复制在肝癌发生中的分子机制；（3）探讨在小鼠肝癌模型中靶向PARG的治疗效果。本项目有望阐明PARG在肝癌中的生物学功能，并为肝癌临床药物的开发提供新的作用靶点和治疗策略。

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. It has insidious onset, rapid progression and poor prognosis, which seriously threatens human health and lacks effective therapeutic strategies. Maintaining the stability of DNA replication forks and repairing the damage caused by replication stress are important regulatory mechanisms of hepatocellular carcinoma, yet key factors have not been found. Poly (ADP-ribose) hydrolase (PARG) is a protease involved in DNA replication and damage repair and is abnormally highly expressed in a variety of tumors. However, the role of PARG in hepatocellular carcinoma have not yet been reported. Our previous studies have shown that PARG is overexpressed in hepatocellular carcinoma patients, and inhibition of PARG could block liver cancer cells in S phase and inhibit liver cancer cells DNA replication. This project intends to explore the biological functions and mechanisms of PARG in hepatocellular carcinoma: (1) determine the role of PARG in DNA replication and liver cancer cells; (2) reveal the molecular mechanism of DNA replication regulated by PARG in hepatocellular carcinoma; (3) explore the therapeutic effect of targeting PARG in liver cancer mice model. This study is expected to clarify the biological function of PARG in hepatocellular carcinoma and provide new targets and therapeutic strategies for development of clinical drugs for hepatocellular carcinoma.