期刊论文详细信息
BMC Cancer
High expression of ubiquitin-conjugating enzyme 2C (UBE2C) correlates with nasopharyngeal carcinoma progression
Zhihua Shen2  Xiaofan Jiang2  Chao Zeng2  Shaojiang Zheng1  Botao Luo2  Yumei Zeng3  Ranran Ding2  Hanguo Jiang2  Qiyi He1  Junli Guo1  Wei Jie2 
[1] Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, 571199, People’s Republic of China
[2] Department of Pathology & Pathophysiology, School of Basic Medicine Science, Guangdong Medical College, Zhanjiang, 524023, People’s Republic of China
[3] Department of Pathology, People’s Hospital of Zhongshan City, Zhongshan, 528400, People’s Republic of China
关键词: Cell cycle;    Proliferation;    Progression;    Ubiquitin-conjugating enzyme 2C;    Nasopharyngeal carcinoma;   
Others  :  1079799
DOI  :  10.1186/1471-2407-13-192
 received in 2013-01-15, accepted in 2013-04-12,  发布年份 2013
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【 摘 要 】

Background

Overexpression of ubiquitin-conjugating enzyme 2C (UBE2C) has been detected in many types of human cancers, and is correlated with tumor malignancy. However, the role of UBE2C in human nasopharyngeal carcinoma (NPC) is unclear. In this study, we investigated the role of aberrant UBE2C expression in the progression of human NPC.

Methods

Immunohistochemical analysis was performed to detect UBE2C protein in clinical samples of NPC and benign nasopharyngeal tissues, and the association of UBE2C expression with patient clinicopathological characteristics was analyzed. UBEC2 expression profiles were evaluated in cell lines representing varying differentiated stages of NPC and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. Furthermore, UBE2C was knocked down using RNA interference in these cell lines and proliferation and cell cycle distribution was investigated.

Results

Immunohistochemical analysis revealed that UBE2C protein expression levels were higher in NPC tissues than in benign nasopharyngeal tissues (P<0.001). Moreover, high UBE2C protein expression was positively correlated with tumor size (P=0.017), lymph node metastasis (P=0.016) and distant metastasis (P=0.015) in NPC patients. In vitro experiments demonstrated that UBE2C expression levels were inversely correlated with the degree of differentiation of NPC cell lines, whereas UBE2C displayed low level of expression in NP-69 cells. Knockdown of UBE2C led to significant arrest at the S and G2/M phases of the cell cycle, and decreased cell proliferation was observed in poorly-differentiated CNE2Z NPC cells and undifferentiated C666-1 cells, but not in well-differentiated CNE1 and immortalized NP-69 cells.

Conclusions

Our findings suggest that high expression of UBE2C in human NPC is closely related to tumor malignancy, and may be a potential marker for NPC progression.

【 授权许可】

   
2013 Shen et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Hershko A, Ciechanover A: The ubiquitin system. Annu Rev Biochem 1998, 67:425-479.
  • [2]Townsley FM, Aristarkhov A, Beck S, Hershko A, Ruderman JV: Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase. Proc Natl Acad Sci U S A 1997, 94:2362-2367.
  • [3]Lin Y, Hwang WC, Basavappa R: Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10. J Biol Chem 2002, 277:21913-21921.
  • [4]Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A: UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. Cancer Res 2003, 63:4167-4173.
  • [5]Hao Z, Zhang H, Cowell J: Ubiquitin-conjugating enzyme UBE2C: molecular biology, role in tumorigenesis, and potential as a biomarker. Tumour Biol 2012, 33:723-730.
  • [6]Ieta K, Ojima E, Tanaka F, Nakamura Y, Haraguchi N, Mimori K, Inoue H, Kuwano H, Mori M: Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression. Int J Cancer 2007, 121:33-38.
  • [7]Pallante P, Berlingieri MT, Troncone G, Kruhoffer M, Orntoft TF, Viglietto G, Caleo A, Migliaccio I, Decaussin-Petrucci M, Santoro M, Palombini L, Fusco A: UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas. Br J Cancer 2005, 93:464-471.
  • [8]Berlingieri MT, Pallante P, Sboner A, Barbareschi M, Bianco M, Ferraro A, Mansueto G, Borbone E, Guerriero E, Troncone G, Fusco A: UbcH10 is overexpressed in malignant breast carcinomas. Eur J Cancer 2007, 43:2729-2735.
  • [9]Fujita T, Ikeda H, Taira N, Hatoh S, Naito M, Doihara H: Overexpression of UbcH10 alternates the cell cycle profile and accelerate the tumor proliferation in colon cancer. BMC Cancer 2009, 9:87. BioMed Central Full Text
  • [10]Chen S, Chen Y, Hu C, Jing H, Cao Y, Liu X: Association of clinicopathological features with UbcH10 expression in colorectal cancer. J Cancer Res Clin Oncol 2010, 136:419-426.
  • [11]Bose MV, Gopal G, Selvaluxmy G, Rajkumar T: Dominant negative Ubiquitin-conjugating enzyme E2C sensitizes cervical cancer cells to radiation. Int J Radiat Biol 2012, 88:629-634.
  • [12]Perrotta I, Bruno L, Maltese L, Russo E, Donato A, Donato G: Immunohistochemical analysis of the ubiquitin-conjugating enzyme UbcH10 in lung cancer: a useful tool for diagnosis and therapy. J Histochem Cytochem 2012, 60:359-365.
  • [13]Jiang L, Huang CG, Lu YC, Luo C, Hu GH, Liu HM, Chen JX, Han HX: Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors. Brain Res 2008, 1201:161-166.
  • [14]Chen SM, Jiang CY, Wu JY, Liu B, Chen YJ, Hu CJ, Liu XX: RNA interference-mediated silencing of UBCH10 gene inhibits colorectal cancer cell growth in vitro and in vivo. Clin Exp Pharmacol Physiol 2010, 37:525-529.
  • [15]Jiang L, Bao Y, Luo C, Hu G, Huang C, Ding X, Sun K, Lu Y: Knockdown of ubiquitin-conjugating enzyme E2C/UbcH10 expression by RNA interference inhibits glioma cell proliferation and enhances cell apoptosis in vitro. J Cancer Res Clin Oncol 2010, 136:211-217.
  • [16]van Ree JH, Jeganathan KB, Malureanu L, van Deursen JM: Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation. J Cell Biol 2010, 188:83-100.
  • [17]Cao SM, Simons MJ, Qian CN: The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer 2011, 30:114-119.
  • [18]Ho FC, Tham IW, Earnest A, Lee KM, Lu JJ: Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence. BMC Cancer 2012, 12:98. BioMed Central Full Text
  • [19]Cho WC: Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer 2007, 6:1.
  • [20]Donato G, Iofrida G, Lavano A, Volpentesta G, Signorelli F, Pallante PL, Berlingieri MT, Pierantoni MG, Palmieri D, Conforti F, Maltese L, Tucci L, Amorosi A, Fusco A: Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors. Clin Neuropathol 2008, 27:219-223.
  • [21]Jie W, He QY, Luo BT, Zheng SJ, Kong YQ, Jiang HG, Li RJ, Guo JL, Shen ZH: Inhibition of Pim-1 attenuates the proliferation and migration in nasopharyngeal carcinoma cells. Asian Pac J Trop Med 2012, 5:645-650.
  • [22]Fang W, Li X, Jiang Q, Liu Z, Yang H, Wang S, Xie S, Liu Q, Liu T, Huang J, Xie W, Li Z, Zhao Y, Wang E, Marincola FM, Yao K: Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. J Transl Med 2008, 6:32. BioMed Central Full Text
  • [23]Takahashi Y, Ishii Y, Nishida Y, Ikarashi M, Nagata T, Nakamura T, Yamamori S, Asai S: Detection of aberrations of ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH. Cancer Genet Cytogenet 2006, 168:30-35.
  • [24]Berlingieri MT, Pallante P, Guida M, Nappi C, Masciullo V, Scambia G, Ferraro A, Leone V, Sboner A, Barbareschi M, Ferro A, Troncone G, Fusco A: UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas. Oncogene 2007, 26:2136-2140.
  • [25]Lin J, Raoof DA, Wang Z, Lin MY, Thomas DG, Greenson JK, Giordano TJ, Orringer MB, Chang AC, Beer DG, Lin L: Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma. Neoplasia 2006, 8:1062-1071.
  • [26]Rajkumar T, Sabitha K, Vijayalakshmi N, Shirley S, Bose MV, Gopal G, Selvaluxmy G: Identification and validation of genes involved in cervical tumourigenesis. BMC Cancer 2011, 11:80. BioMed Central Full Text
  • [27]Troncone G, Guerriero E, Pallante P, Berlingieri MT, Ferraro A, Del Vecchio L, Gorrese M, Mariotti E, Iaccarino A, Palmieri EA, Zeppa P, Palombini L, Fusco A: UbcH10 expression in human lymphomas. Histopathology 2009, 54:731-740.
  • [28]Psyrri A, Kalogeras KT, Kronenwett R, Wirtz RM, Batistatou A, Bournakis E, Timotheadou E, Gogas H, Aravantinos G, Christodoulou C, Makatsoris T, Linardou H, Pectasides D, Pavlidis N, Economopoulos T, Fountzilas G: Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) study. Ann Oncol 2012, 23:1422-1427.
  • [29]Vasiljevic A, Champier J, Figarella-Branger D, Wierinckx A, Jouvet A, Fevre-Montange M: Molecular characterization of central neurocytomas: potential markers for tumor typing and progression. Neuropathology 2013, 33:149-161.
  • [30]Bavi P, Uddin S, Ahmed M, Jehan Z, Bu R, Abubaker J, Sultana M, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F, Prabhakaran S, Hussain AR, Al-Kuraya KS: Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of UBE2C in colorectal carcinoma. Am J Pathol 2011, 178:2109-2120.
  • [31]Wagner KW, Sapinoso LM, El-Rifai W, Frierson HF, Butz N, Mestan J, Hofmann F, Deveraux QL, Hampton GM: Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. Oncogene 2004, 23:6621-6629.
  • [32]Wang H, Zhang C, Rorick A, Wu D, Chiu M, Thomas-Ahner J, Chen Z, Chen H, Clinton SK, Chan KK, Wang Q: CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability. Cancer Res 2011, 71:4866-4876.
  • [33]Lee JJ, Au AY, Foukakis T, Barbaro M, Kiss N, Clifton-Bligh R, Staaf J, Borg A, Delbridge L, Robinson BG, Wallin G, Hoog A, Larsson C: Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma. Endocr Relat Cancer 2008, 15:801-815.
  • [34]Tzelepi V, Zhang J, Lu JF, Kleb B, Wu G, Wan X, Hoang A, Efstathiou E, Sircar K, Navone NM, Troncoso P, Liang S, Logothetis CJ, Maity SN, Aparicio AM: Modeling a lethal prostate cancer variant with small-cell carcinoma features. Clin Cancer Res 2012, 18:666-677.
  • [35]Lo KW, Chung GT, To KF: Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol 2012, 22:79-86.
  • [36]Li X, Wang E, Zhao YD, Ren JQ, Jin P, Yao KT, Marincola FM: Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of comparative genomic hybridization results. J Transl Med 2006, 4:4. BioMed Central Full Text
  • [37]Lo KW, Teo PM, Hui AB, To KF, Tsang YS, Chan SY, Mak KF, Lee JC, Huang DP: High resolution allelotype of microdissected primary nasopharyngeal carcinoma. Cancer Res 2000, 60:3348-3353.
  • [38]Hu C, Wei W, Chen X, Woodman CB, Yao Y, Nicholls JM, Joab I, Sihota SK, Shao JY, Derkaoui KD, Amari A, Maloney SL, Bell AI, Murray PG, Dawson CW, Young LS, Arrand JR: A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels. PLoS One 2012, 7:e41055.
  • [39]Yan W, Song L, Wei W, Li A, Liu J, Fang Y: Chromosomal abnormalities associated with neck nodal metastasis in nasopharyngeal carcinoma. Tumour Biol 2005, 26:306-312.
  • [40]Patle D, McCance DJ: Compromised spindle assembly checkpoint due to altered expression of Ubch10 and Cdc20 in human papillomavirus type 16 E6- and E7-expressing keratinocytes. Virol 2010, 84:10956-10964.
  • [41]Deng W, Pang PS, Tsang CM, Hau PM, Yip YL, Cheung AL, Tsao SW: Epstein-Barr virus-encoded latent membrane protein 1 impairs G2 checkpoint in human nasopharyngeal epithelial cells through defective Chk1 activation. PLoS One 2012, 7:e39095.
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