Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma

PURPOSE: O-linked N-acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers. The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC). METHODS: O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try. Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay. A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells. Cell apoptosis and cell cycle assays were performed by flow cytometry. Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR. RESULTS: O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis. OGT knockdown significantly suppressed RCC cell proliferation in vitro and in vivo. Notably, EGFR was modulated by O-GlcNAcylation and directly interacted with OGT. CONCLUSION: These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.