O-GlcNAcylation Enhances NUSAP1 Stability and Promotes Bladder Cancer Aggressiveness

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2021 Jan 25

PMID 33488099

Citations 11

Authors

Yifan Chen

Ji Liu

Wentao Zhang

Aimaitiaji Kadier

Ruiliang Wang

Haimin Zhang

Xudong Yao

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

NUSAP1 is Upregulated by Estrogen to Promote Lung Adenocarcinoma Growth and Serves as a Therapeutic Target.

Zhang S, Zhang X, Huang W, Jiang G, Mo Y, Wei L Int J Biol Sci. 2024; 20(13):5375-5395.

PMID: 39430250 PMC: 11489181. DOI: 10.7150/ijbs.100188.

The roles of OGT and its mechanisms in cancer.

Liu X, Wang J, Xiang Y, Wang K, Yan D, Tong Y Cell Biosci. 2024; 14(1):121.

PMID: 39285476 PMC: 11406787. DOI: 10.1186/s13578-024-01301-w.

NUSAP1 promotes gastric cancer radioresistance by inhibiting ubiquitination of ANXA2 and is suppressed by miR-129-5p.

Ge Y, Wang B, Xiao J, Wu H, Shao Q J Cancer Res Clin Oncol. 2024; 150(8):406.

PMID: 39212774 PMC: 11364566. DOI: 10.1007/s00432-024-05927-8.

Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer.

Li H, Bao X, Xiao Y, Yin H, Han X, Kang S Transl Cancer Res. 2024; 13(2):579-593.

PMID: 38482431 PMC: 10928602. DOI: 10.21037/tcr-23-1770.

Altered Glycosylation in Progression and Management of Bladder Cancer.

Wilczak M, Surman M, PRZYBYlO M Molecules. 2023; 28(8).

PMID: 37110670 PMC: 10146225. DOI: 10.3390/molecules28083436.

References

Raemaekers T, Ribbeck K, Beaudouin J, Annaert W, Van Camp M, Stockmans I . NuSAP, a novel microtubule-associated protein involved in mitotic spindle organization. J Cell Biol. 2003; 162(6):1017-29. PMC: 2172854. DOI: 10.1083/jcb.200302129. View

Torres C, Hart G . Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J Biol Chem. 1984; 259(5):3308-17. View

Wu X, Xu B, Yang C, Wang W, Zhong D, Zhao Z . Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway. J Exp Clin Cancer Res. 2017; 36(1):127. PMC: 5596921. DOI: 10.1186/s13046-017-0597-y. View

Trinca G, Goodman M, Papachristou E, DSantos C, Chalise P, Madan R . O-GlcNAc-Dependent Regulation of Progesterone Receptor Function in Breast Cancer. Horm Cancer. 2017; 9(1):12-21. PMC: 5775912. DOI: 10.1007/s12672-017-0310-9. View

Butkinaree C, Park K, Hart G . O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. Biochim Biophys Acta. 2009; 1800(2):96-106. PMC: 2815129. DOI: 10.1016/j.bbagen.2009.07.018. View

Chen L, Yang L, Qiao F, Hu X, Li S, Yao L . High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer. PLoS One. 2015; 10(10):e0140572. PMC: 4618922. DOI: 10.1371/journal.pone.0140572. View

Chen D, Nasir A, Culhane A, Venkataramu C, Fulp W, Rubio R . Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue. Breast Cancer Res Treat. 2009; 119(2):335-46. PMC: 2796276. DOI: 10.1007/s10549-009-0344-y. View

Rozanski W, Krzeslak A, Forma E, Brys M, Blewniewski M, Wozniak P . Prediction of bladder cancer based on urinary content of MGEA5 and OGT mRNA level. Clin Lab. 2012; 58(5-6):579-83. View

Zachara N, Hart G . O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress. Biochim Biophys Acta. 2004; 1673(1-2):13-28. DOI: 10.1016/j.bbagen.2004.03.016. View

10.

Shi Y, Tomic J, Wen F, Shaha S, Bahlo A, Harrison R . Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia. 2010; 24(9):1588-98. PMC: 4361888. DOI: 10.1038/leu.2010.152. View

11.

Ribbeck K, Groen A, Santarella R, Bohnsack M, Raemaekers T, Kocher T . NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules. Mol Biol Cell. 2006; 17(6):2646-60. PMC: 1474800. DOI: 10.1091/mbc.e05-12-1178. View

12.

Gordon C, Gulzar Z, Brooks J . NUSAP1 expression is upregulated by loss of RB1 in prostate cancer cells. Prostate. 2015; 75(5):517-26. DOI: 10.1002/pros.22938. View

13.

Kokkinakis D, Liu X, Neuner R . Modulation of cell cycle and gene expression in pancreatic tumor cell lines by methionine deprivation (methionine stress): implications to the therapy of pancreatic adenocarcinoma. Mol Cancer Ther. 2005; 4(9):1338-48. DOI: 10.1158/1535-7163.MCT-05-0141. View

14.

Okamoto A, Higo M, Shiiba M, Nakashima D, Koyama T, Miyamoto I . Down-Regulation of Nucleolar and Spindle-Associated Protein 1 (NUSAP1) Expression Suppresses Tumor and Cell Proliferation and Enhances Anti-Tumor Effect of Paclitaxel in Oral Squamous Cell Carcinoma. PLoS One. 2015; 10(11):e0142252. PMC: 4640814. DOI: 10.1371/journal.pone.0142252. View

15.

Wang L, Liu J, Zhang P, An M, Han C, Li Y . O-GlcNAcylation modulates Bmi-1 protein stability and potential oncogenic function in prostate cancer. Oncogene. 2017; 36(45):6293-6305. DOI: 10.1038/onc.2017.223. View

16.

Kamigaito T, Okaneya T, Kawakubo M, Shimojo H, Nishizawa O, Nakayama J . Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. Prostate Cancer Prostatic Dis. 2013; 17(1):18-22. DOI: 10.1038/pcan.2013.56. View

17.

Gordon C, Gong X, Ganesh D, Brooks J . NUSAP1 promotes invasion and metastasis of prostate cancer. Oncotarget. 2017; 8(18):29935-29950. PMC: 5444715. DOI: 10.18632/oncotarget.15604. View

18.

Satow R, Shitashige M, Kanai Y, Takeshita F, Ojima H, Jigami T . Combined functional genome survey of therapeutic targets for hepatocellular carcinoma. Clin Cancer Res. 2010; 16(9):2518-28. DOI: 10.1158/1078-0432.CCR-09-2214. View

19.

Ma Z, Vosseller K . O-GlcNAc in cancer biology. Amino Acids. 2013; 45(4):719-33. DOI: 10.1007/s00726-013-1543-8. View

20.

Srikanth B, Vaidya M, Kalraiya R . O-GlcNAcylation determines the solubility, filament organization, and stability of keratins 8 and 18. J Biol Chem. 2010; 285(44):34062-71. PMC: 2962505. DOI: 10.1074/jbc.M109.098996. View