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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

25卷

期数:

2019年04期

页码:

373-377

栏目:

临床医学

出版日期:

2019-07-20

文章信息/Info

Title:

The characteristics of SOX6 in development of bladder cancer and relevant mechanism

文章编号:

1006-8147(2019)04-0373-05

作者:

付真睿; 盛 飞; 张昌文; 常泰浩; 陈仕洋; 乔宝民

（天津医科大学第二医院泌尿外科，天津市泌尿外科研究所，天津 300211）

Author(s):

FU Zhen-rui;  SHENG Fei;  ZHANG Chang-wen;  CHANG Tai-hao;  CHEN Shi-yang;  QIAO Bao-min

(Department of Urology, The Second Hospital, Tianjin Medical University,Tianjin Institute of Urology, Tianjin 300211, China)

关键词:

膀胱癌; SOX6; 上皮间质转化; 20 s蛋白酶体

Keywords:

Bladder cancer;  SOX6;  Epithelial-mesenchymal transition;  20 s proteasome

分类号:

R737.14

DOI:

-

文献标志码:

A

摘要:

目的：研究SOX6在膀胱癌中的表达特征，并探讨其在膀胱癌中发挥的生物学效应及相关机制。方法：利用免疫组化检测膀胱癌组织和癌旁组织中的SOX6的表达，蛋白印记（Western blot）及荧光实时定量PCR（qRT-PCR）检测SOX6在膀胱癌细胞（T24、BIU-87、EJ、5637）和正常膀胱上皮细胞（SV-HUC-1）中表达情况。通过SOX6高表达质粒和空载质粒分别转染膀胱癌细胞（EJ、5637），使用Transwell方法检测两组细胞的侵袭能力，采用划痕实验检测迁移能力，Western blot法检测E-cadherin和Vimentin的表达，使用CCK-8实验检测两组细胞的增殖能力，流式细胞术检测凋亡情况，并研究对膀胱癌细胞的蛋白酶体活性的影响。结果：与癌旁组织和正常膀胱上皮细胞相比，膀胱癌组织和细胞中SOX6的表达显著下降，在细胞EJ和5637尤其明显。与对照组对比，转染SOX6高表达质粒的EJ 和5637膀胱癌细胞的迁移、侵袭、增殖能力减弱，凋亡增加，上皮间质转化能力减弱，同时蛋白酶体活性显著降低。结论：SOX6在膀胱癌中作为抑癌基因发生作用，通过降低蛋白酶体活性来抑制膀胱癌的发展。

Abstract:

Objective: To investigate the expression and biological effects of SOX6 in bladder cancer and its molecular mechanisms.Methods: The expression of SOX6 in bladder cancer tissues and paracancerous tissues was detected by immunohistochemistry, western blot and real-time quantitative PCR (qRT-PCR) were used to explore the expression of SOX6 in bladder cancer cell lines (T24, BIU-87, EJ, 5637) and normal bladder epithelial cells (SV-HUC-1) was detected.SOX6 high expression plasmid and empty plasmid were transfected into bladder cancer cells (EJ, 5637), respectively.Transwell assay was used to detect the invasion,and scratch test was used to determine migration ability. Western blot was used to test the expression of E-cadherin and Vimentin. Theproliferation of cells was validated by CCK-8 assay, and the apoptosis was detected by flow cytometry. Furthermore, the influence on proteasome was also studied in bladder cancer cell. Results: Compared with paracancerous tissues and normal bladder epithelial cells, the expression of SOX6 in bladder cancer tissues and cells was significantly decreased, especially in cancer cell lines EJ and 5637. Compared with the control group, after overexpression of SOX6, the cell migration, invasion, and proliferation were lessened, the percentage apoptosis was increased, and epithelial-mesenchymal transition was reduced. Meanwhile, the activity of proteasome was also significantly decreased. Conclusions: SOX6 may function as a tumor suppressor gene in bladder cancer and may inhibit the development of bladder cancer by reducing proteasome activity.

参考文献/References:

[1] Siegel R L, Miller K D, Jemal A. Cancer Statistics, 2017[J]. CA Cancer J Clin, 2017, 67(1): 7
[2] Kamat A M, Hahn N M, Efstathiou J A, et al. Bladder cancer[J]. Lancet (London, England), 2016, 388(10061): 2796
[3] Rose T L, Milowsky M I. Improving Systemic Chemotherapy for Bladder Cancer [J]. Curr Oncol Rep, 2016, 18(5): 27
[4] Kamachi Y, Kondoh H. Sox proteins: regulators of cell fate specification and differentiation[J]. Development (Cambridge, England), 2013, 140(20): 4129
[5] Sarkar A, Hochedlinger K. The sox family of transcription factors: versatile regulators of stem and progenitor cell fate[J]. Cell stem cell, 2013, 12(1): 15
[6] Li Y, Xiao M, Guo F. The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis[J]. Tumour Biol，2017, 39(5): 1010428317705508
[7] Yu Y, Wang Z, Sun D, et al. miR-671 promotes prostate cancer cell proliferation by targeting tumor suppressor SOX6[J]. Eur J Pharmacol, 2018, 823：65
[8] Qin Y R, Tang H, Xie F, et al. Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma [J]. Clin Cancer Res, 2011, 17(1): 46
[9] Jiang W, Yuan Q, Jiang Y, et al. Identification of Sox6 as a regulator of pancreatic cancer development[J]. J Cell Mol Med, 2018, 22(3): 1864
[10] 刘恩令,周玉秀,王立群，等. 过表达SOX6基因对卵巢癌SKOV3细胞增殖、凋亡的影响及其机制[J].山东医药, 2018, 58(20):39
[11] Wang Z, Li J, Li K, et al. SOX6 is downregulated in osteosarcoma and suppresses the migration, invasion and epithelial-mesenchymal transition via TWIST1 regulation [J]. Mol Med Rep, 2018, 17(5): 6803
[12] Li Y C, Li C F, Chen L B, et al. MicroRNA-766 targeting regulation of SOX6 expression promoted cell proliferation of human colorectal cancer [J]. Onco Targets Ther, 2015, 8：2981
[13] Elenich L A, Nandi D, Kent A E, et al. The complete primary structure of mouse 20S proteasomes[J]. Immunogenetics, 1999, 49(10): 835
[14] Mittenberg A G, Moiseeva T N, Kuzyk V O, et al. Mass-spectrometric analysis of proteasomal subunits possessing endoribonuclease activity[J]. Tsitologiia, 2014, 56(4): 300
[15] Li Y, Huang J, Sun J, et al. The transcription levels and prognostic values of seven proteasome alpha subunits in human cancers[J]. Oncotarget, 2017, 8(3): 4501
[16] Collins G A, Goldberg A L. The Logic of the 26S Proteasome[J]. Cell, 2017, 169(5): 792
[17] Voutsadakis I A, Papandreou C N. The ubiquitin-proteasome system in prostate cancer and its transition to castration resistance[J]. Urol Oncol, 2012, 30(6): 752

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备注/Memo

备注/Memo:

作者简介 付真睿（1993-），男，硕士在读，研究方向：泌尿外科；通信作者：乔宝民，E-mail：qbm2000@163.com。

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更新日期/Last Update: 2019-08-28