High expression of ubiquitin-conjugating enzyme 2C (UBE2C) correlates with nasopharyngeal carcinoma progression

Zhihua Shen,Ranran Ding,Wei Jie,Shaojiang Zheng,Hanguo Jiang,Botao Luo,Qiyi He,Xiaofan Jiang,Yumei Zeng,Chao Zeng,Junli Guo

doi:10.1186/1471-2407-13-192

Zhihua Shen, Ranran Ding + Show 9 more

Open Access

https://doi.org/10.1186/1471-2407-13-192

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Abstract

BackgroundOverexpression 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.MethodsImmunohistochemical 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.ResultsImmunohistochemical 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.ConclusionsOur 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.

Highlights

Overexpression of ubiquitin-conjugating enzyme 2C (UBE2C) has been detected in many types of human cancers, and is correlated with tumor malignancy
Immunohistochemical analysis of UBE2C protein expression in nasopharyngeal carcinoma (NPC) and nasopharyngeal tissues First, we investigated the expression of UBE2C in nasopharyngeal epithelial hyperplasia (NEH) and NPC
In the present study, we first found that UBE2C was predominantly expressed in NPC samples, whereas it was weakly expressed in nasopharyngeal tissues; we found that high UBE2C protein expression was positively related to tumor size, lymph node metastasis and distant metastasis in NPC patients

Summary

Introduction

Overexpression of ubiquitin-conjugating enzyme 2C (UBE2C) has been detected in many types of human cancers, and is correlated with tumor malignancy. In 2003, Okamoto et al demonstrated that UBE2C expression levels were extremely low in many normal tissues, but prominent in the majority of cancerous cell lines examined, suggesting that UBE2C has the ability to promote cell proliferation and malignant transformation [4]. UBE2C transgenic mice are prone to carcinogen-induced lung tumors and a broad spectrum of spontaneous tumors, as UBE2C is a prominent proto-oncogene [16]. Taken together, these data suggest that targeting of UBE2C may be a potential tool for tumor diagnosis and therapy

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