O-GlcNAcylation promotes malignant phenotypes of bladder cancer cells

Lu Jin, Mei-Hua Lu, Guang-Cheng Dai, Qiu Yao, Han Xiang, Li-Xia Wang, Bo-Xin Xue,  Xiaolong Liu

Abstract:

O-GlcNAcylation (O-GlcNAc) is a posttranslational modification that is mediated by O-GlcNAc-transferase (OGT) and reversed by O-GlcNAcase (OGA). Increasing evidence indicates that protein O-GlcNAcylation is increased in various types of cancer. In the present study, we aimed to evaluate the expression and function of both OGT and OGA in bladder cancer cells in vitro and in vivo. Expression data of OGT and OGA at the mRNA level was obtained from the Oncomine database. Effects of OGT and OGA on cell proliferate, invasive, and migratory abilities were assessed using MTT, wound healing, cell invasive assay, and cell cycle analysis. In vivo assay was also performed in nude mice. The results revealed that the expression of OGT in bladder cancer tissues was higher than that of normal tissues, while the OGA level was found to be lower in cancer tissues. We also found that knockdown of OGT could inhibit cell proliferation, migration, invasion, and induce cell cycle arrest, while these are reversed when OGA is inhibited. We also observed that O-GlcNAcylation could promote tumor formation in vivo, compared with a negative control. In summary, this study describes the oncogenic role of O-GlcNAcylation in bladder cancer cells.