肿瘤的发生发展常伴随能量代谢异常，其中氨基己糖生物合成途径能够使多种细胞内蛋白发生O-GlcNAc修饰，参与肿瘤发生。在肝细胞肝癌中，p27kip1是负性调节肿瘤发生与进程的重要蛋白。课题组前期研究发现p27kip1可发生O-GlcNAc修饰，进一步鉴定p27kip1的Ser2是其糖基化修饰位点。鉴于此提出p27kip1的O-GlcNAc修饰，调控p27kip1基因表达和影响HCC发生发展的假说。本课题拟先明确p27kip1能够发生O-GlcNAc修饰；接着分析p27kip1发生O-GlcNAc修饰后对磷酸化水平的影响及对磷酸化信号转导途径的影响；进一步分析p27kip1的O-GlcNAc修饰对肝癌细胞的增殖和恶变的影响；最后分析干预p27kip1的O-GlcNAc修饰在HCC发生发展中的意义。本项目研究为阐明HCC的发生机制，寻找HCC治疗靶点提供理论依据和方法支持。

The occurrence and development of tumor is often accompanied by abnormal energy metabolism. Multiple intracellular proteins are modified with O-GlcNAc through HBP (hexosamine biosynthesis pathway). p27kip1 plays an important regulatory role in cell proliferation, differentiation and malignant transformation in hepatocellular carcinoma. Our groups found that p27kip1 is O-GlcNAc modified, further research identified Ser2 as the glycosylation site of p27kip1. So we hypothesized p27kip1 O-GlcNAc modification affect HCC development via affecting p27kip1 gene expression. In this project, we intend to first prove that p27kip1 is O-GlcNAc modified. Secondly, we investigated the influence of O-GlcNAcylation on phosphorylation level. Thirdly, we analized the effects of O-GlcNAcylation on signal transduction pathway and investigated its effect on HCC proliferation. The project study provides experimental and theoretical basis for elucidation the pathogenesis of HCC, looking for its therapeutic targets.