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O-GlcNAcylation Enhances NUSAP1 Stability and Promotes Bladder Cancer Aggressiveness

Authors Chen Y, Liu J, Zhang W, Kadier A, Wang R, Zhang H, Yao X

Received 20 May 2020

Accepted for publication 24 December 2020

Published 15 January 2021 Volume 2021:14 Pages 445—454

DOI https://doi.org/10.2147/OTT.S258175

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Gaetano Romano


Yifan Chen,* Ji Liu,* Wentao Zhang, Aimaitiaji Kadier,* Ruiliang Wang, Haimin Zhang, Xudong Yao

Department of Urology, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai, 200072, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xudong Yao; Haimin Zhang
Department of Urology, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, People’s Republic of China
Email yaoxudong1967@163.com; zhm1064@163.com

Objective: NUSAPl and O-GlcNAcylation were reported to be hyper-activated in many kinds of cancers and involved in the advanced progression of cancers. In bladder cancer, O-GlcNAc transferase (OGT) expresses in patients’ urine samples, with no expression in healthy individuals, indicating O-GlcNAcylation might involve in the occurrence and development of bladder cancer. Therefore, the present study aims to investigate the effects of O-GlcNAcylation in bladder cancer and if it can regulate NUSAP1 protein.
Materials and Methods: Western blot, immunohistochemistry, and PCR were used to evaluate the protein expression and mRNA level of NUSAP1; CCK-8 and flow cytometry used to evaluate the proliferation and inhibited the apoptosis of bladder cancer.
Results: The results showed that NUSAP1 was highly expressed in bladder cancer cells and tissue samples. NUSAP1 up-regulation significantly promoted the proliferation and inhibited the apoptosis of bladder cancer HT-1376 and T24 cells. Besides, the expression of O-GlcNAc was elevated in bladder cancer tissues and cells, and up-regulation of O-GlcNAc with GlcNAc and PuGNAc obviously increased NUSAP1 protein expression and stability. Moreover, knockdown OGT significantly inhibited the proliferation and tumorigenesis and promoted the apoptosis of bladder cancer cells, confirmed by CCK-8, in vivo xenotransplantation, and flow cytometry, whereas these roles were impaired when NUSAP1 was up-regulated.
Conclusion: Overall, our study makes clear that hyper-O-GlcNAcylation accelerates bladder cancer progression through promotion of NUSAP1 expression and its stability.

Keywords: NUSAP1, O-GlcNAcylation, stability, bladder cancer, aggressiveness

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