UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells

Gong,Yan  Qing; Peng,Ding; Ning,Xiang  Hui; Yang,Xin  Yu; Li,Xue  Song; Zhou,Li  Qun; Guo,Ying  Lu

doi:10.3892/ol.2016.5237

UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells

Authors:
- Yan Qing Gong
- Ding Peng
- Xiang Hui Ning
- Xin Yu Yang
- Xue Song Li
- Li Qun Zhou
- Ying Lu Guo
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Affiliations: Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China
Published online on: October 10, 2016 https://doi.org/10.3892/ol.2016.5237
Pages: 4485-4492
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the ubiquitin-conjugating E2 family in the ubiquitin-proteasome pathway, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. In the present study, the expression of UBE2T and its association with bladder cancer were investigated; to the best of our knowledge, this has not been reported previously. Immunohistochemistry and western blot analysis demonstrated that UBE2T was significantly upregulated in bladder cancer tissues and cell lines compared with adjacent normal bladder tissues and a normal human urinary tract epithelial cell line, respectively. UBE2T was detectable in the nuclei and cytoplasm of cancer cells, exhibiting stronger expression in the nuclei. A UBE2T‑siRNA‑expressing lentivirus was constructed and used to infect human bladder cancer 5637 cells, in order to examine the role of UBE2T in bladder cancer cell growth in vitro. The knockdown of UBE2T significantly decreased bladder cancer cell proliferation and colony formation. Furthermore, UBE2T silencing induced cell cycle arrest at G2/M phase and increased cell apoptosis. Therefore, UBE2T serves an important role in the growth of bladder cancer cells, and may be considered as a potential biomarker and therapeutic target for bladder cancer.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS and Jemal A: Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 64:252–271. 2014. View Article : Google Scholar : PubMed/NCBI
3	Markson G, Kiel C, Hyde R, Brown S, Charalabous P, Bremm A, Semple J, Woodsmith J, Duley S, Salehi-Ashtiani K, et al: Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res. 19:1905–1911. 2009. View Article : Google Scholar : PubMed/NCBI
4	Shekhar MP, Lyakhovich A, Visscher DW, Heng H and Kondrat N: Rad6 overexpression induces multinucleation, centrosome amplification, abnormal mitosis, aneuploidy, and transformation. Cancer Res. 62:2115–2124. 2002.PubMed/NCBI
5	Dong M, Pang X, Xu Y, Wen F and Zhang Y: Ubiquitin-conjugating enzyme 9 promotes epithelial ovarian cancer cell proliferation in vitro. Int J Mol Sci. 14:11061–11071. 2013. View Article : Google Scholar : PubMed/NCBI
6	Shuliang S, Lei C, Guangwu J and Changjie L: Involvement of ubiquitin-conjugating enzyme E2C in proliferation and invasion of prostate carcinoma cells. Oncol Res. 21:121–127. 2013. View Article : Google Scholar : PubMed/NCBI
7	Xie C, Powell C, Yao M, Wu J and Dong Q: Ubiquitin-conjugating enzyme E2C: A potential cancer biomarker. Int J Biochem Cell Biol. 47:113–117. 2014. View Article : Google Scholar : PubMed/NCBI
8	Hodson C, Purkiss A, Miles JA and Walden H: Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection. Structure. 22:337–344. 2014. View Article : Google Scholar : PubMed/NCBI
9	Ramaekers CH, van den Beucken T, Meng A, Kassam S, Thoms J, Bristow RG and Wouters BG: Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy through regulation of UBE2T. Radiother Oncol. 101:190–197. 2011. View Article : Google Scholar : PubMed/NCBI
10	Ueki T, Park JH, Nishidate T, Kijima K, Hirata K, Nakamura Y and Katagiri T: Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells. Cancer Res. 69:8752–8760. 2009. View Article : Google Scholar : PubMed/NCBI
11	Hao J, Xu A, Xie X, Hao J, Tian T, Gao S, Xiao X and He D: Elevated expression of UBE2T in lung cancer tumors and cell lines. Tumour Biol. 29:195–203. 2008. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
14	Nakayama KI and Nakayama K: Ubiquitin ligases: Cell-cycle control and cancer. Nat Rev Cancer. 6:369–381. 2006. View Article : Google Scholar : PubMed/NCBI
15	Hoeller D, Hecker CM and Dikic I: Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer. 6:776–788. 2006. View Article : Google Scholar : PubMed/NCBI
16	Longerich S, Kwon Y, Tsai MS, Hlaing AS, Kupfer GM and Sung P: Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA. Nucleic Acids Res. 42:5657–5670. 2014. View Article : Google Scholar : PubMed/NCBI
17	Sato K, Toda K, Ishiai M, Takata M and Kurumizaka H: DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI. Nucleic Acids Res. 40:4553–4561. 2012. View Article : Google Scholar : PubMed/NCBI
18	Alpi A, Langevin F, Mosedale G, Machida YJ, Dutta A and Patel KJ: UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: A basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 27:8421–8430. 2007. View Article : Google Scholar : PubMed/NCBI
19	Machida YJ, Machida Y, Chen Y, Gurtan AM, Kupfer GM, D'Andrea AD and Dutta A: UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 23:589–596. 2006. View Article : Google Scholar : PubMed/NCBI
20	Corson TW, Huang A, Tsao MS and Gallie BL: KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers. Oncogene. 24:4741–4753. 2005. View Article : Google Scholar : PubMed/NCBI
21	Wilson WR and Hay MP: Targeting hypoxia in cancer therapy. Nat Rev Cancer. 11:393–410. 2011. View Article : Google Scholar : PubMed/NCBI
22	Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA and Dynlacht BD: E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev. 16:245–256. 2002. View Article : Google Scholar : PubMed/NCBI