Reciprocal Regulation Between O-GlcNAcylation and β-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer
| Autor: | Yan Lin, Yijie Liu, Yun Miao, Pingan Qian, Xingliang Fan, Junfeng Zhu, Sicheng Gao, Po Zhu, Xing Liu, Yaoyao Dai, Li Xia, Jun Zhou |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Carcinogenesis Cell Survival Apoptosis Biology medicine.disease_cause Acetylglucosamine 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Genetics medicine Humans Viability assay Molecular Biology beta Catenin Gene knockdown Cell growth Liver Neoplasms Cancer Hep G2 Cells Cell Biology General Medicine medicine.disease Nucleotidyltransferases Up-Regulation Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Catenin Disease Progression |
| Zdroj: | DNA and Cell Biology. 38:286-296 |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2018.4447 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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