氨基己糖生物合成通路与O-糖基化在肝细胞癌代谢中作用的研究进展

Research progress on the role of hexosamine biosynthesis pathway and O-glycosylation in metabolism of hepatocellular carcinoma

目的总结氨基己糖生物合成通路(HBP)与O-糖基化的特点以及它们在肝细胞癌代谢中的作用。方法复习HBP通路与O-糖基化在肿瘤中尤其是肝细胞癌代谢中的作用及研究现状的文献并予以综述。结果肝细胞癌细胞内存在代谢重编程,HBP属于糖酵解的分支代谢通路,在肿瘤的发生、发展与转移方面起着重要作用。HBP为O-糖基化修饰提供尿苷二磷酸-N-乙酰氨基葡萄糖胺(UDP-GlcNAc),UDP-GlcNAc作为O-链接-N-乙酰葡萄糖胺(O-GlcNAc)转移酶(OGT)催化酶的亚基参与O-糖基化修饰。O-糖基化修饰属于一种翻译后修饰,能够对肿瘤细胞内靶蛋白进行糖基化修饰,从而调控肿瘤细胞的生物学行为。结论HBP与O-糖基化可以作为肝细胞癌治疗的干预靶点,这为肝细胞癌的科学防控与治疗提供了一种潜在的理论基础。

Objective To summarize the characteristics of hexosamine biosynthesis pathway(HBP)and O-glycosylation and their roles in metabolism of hepatocellular carcinoma.Method To review the current literatures on the role of HBP and O-glycosylation in tumors,especially in hepatocellular carcinoma.Results There was metabolic reprogramming in hepatocellular carcinoma cells,and the HBP was a branch of glycolysis pathway,which played an important role in tumorigenesis,development,and metastasis.HBP provided uridine diphosphate-N-acetylglucosamine(UDP-GlcNAc)for O-glycosylation,UDP-GlcNAc was a substrate for OGT,participating in O-glycosylation.O-glycosylation was a type of posttranslational modification that regulates the biological behavior of tumor cells by glycosylation of target proteins in tumor cells.Conclusion HBP and O-glycosylation can be used as intervention targets in the treatment of hepatocellular carcinoma,which provides a potential method for scientific prevention and treatment of hepatocellular carcinoma.