1 Department of Hepatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
2 Department of Rehabilitation, Shanghai General Hospital, Shanghai, P.R. China.
DNA Cell Biol. 2019 Apr;38(4):286-296. doi: 10.1089/dna.2018.4447. Epub 2019 Feb 14.
Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes. In this study, we identified the interaction between O-GlcNAc and β-catenin, and explored their effects on the progression of liver cancer. Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7. In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination. Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells. Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression. In conclusion, this study revealed that the reciprocal regulation between O-GlcNAcylation and β-catenin facilitated the proliferation of liver cancer.
O-连接β-N-乙酰葡萄糖胺（O-GlcNAc）和β-连环蛋白的异常表达是癌症的普遍特征，并有助于转化表型。在这项研究中，我们确定了 O-GlcNAc 与 β-连环蛋白之间的相互作用，并探讨了它们对肝癌进展的影响。我们的结果表明，高葡萄糖诱导 O-GlcNAc 的上调，而 PuGNAc 和 GlcNAc 的应用增加了β-连环蛋白蛋白表达水平，以及在肝癌细胞系 HEP-G2 和 HuH-7 中的蛋白稳定性和核积累。此外，β-连环蛋白的过表达可以通过上调尿嘧啶 5'-二磷酸（UDP）-N-乙酰葡萄糖胺焦磷酸化酶 1（UAP1）蛋白表达、蛋白稳定性和抑制其泛素化来增加 O-GlcNAc 表达水平。此外，β-连环蛋白的 O-GlcNAcylation 促进了 HEP-G2 和 HuH-7 细胞的增殖、集落形成，并抑制了细胞凋亡的诱导。β-连环蛋白的敲低通过下调 UAP1 表达降低了细胞增殖、集落形成和肿瘤发生，并促进了细胞凋亡。总之，这项研究表明 O-GlcNAcylation 和 β-连环蛋白之间的相互调节促进了肝癌的增殖。
