Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma
Authors Wang L, Chen S, Zhang J, Mao S, Mao W, Zhang W, Guo Y, Wu Y, Wang R, Yan Y, Yao X
Received 12 October 2018
Accepted for publication 8 February 2019
Published 19 March 2019 Volume 2019:11 Pages 2215—2223
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr Rituraj Purohit
Longsheng Wang,1 Shaojun Chen,2 Junfeng Zhang,1 Shiyu Mao,1 Weipu Mao,1 Wentao Zhang,1 Yadong Guo,1 Yuan Wu,1 Ruiliang Wang,1 Yang Yan,1 Xudong Yao1
1Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, China; 2Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, China
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 Immunohistochemistry. 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.
Keywords: renal cancer, O-GlcNAcylation, OGT, proliferation, EGFR
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