High expression of ubiquitin-conjugating enzyme 2C (UBE2C) correlates with nasopharyngeal carcinoma progression.
High expression of ubiquitin-conjugating enzyme 2C (UBE2C) correlates with nasopharyngeal carcinoma progression.
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泛素结合酶 2C (UBE2C) 高表达与鼻咽癌进展相关
DOI：
10.1186/1471-2407-13-192
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发表时间：
2013-04-15
期刊：
影响因子：
3.8
通讯作者：
Jie W
中科院分区：
文献类型：
--
作者：
Shen Z;Jiang X;Zeng C;Zheng S;Luo B;Zeng Y;Ding R;Jiang H;He Q;Guo J;Jie W
背景泛素结合酶2C（ubiquitin-conjugating enzyme 2C，UBE 2C）在多种肿瘤中过度表达，并与肿瘤恶性程度相关。然而，UBE 2C在人鼻咽癌（NPC）中的作用尚不清楚。本研究旨在探讨UBE 2C在鼻咽癌组织中的异常表达及其在鼻咽癌发生发展中的作用。方法采用免疫组化方法检测UBE 2C在鼻咽癌及鼻咽良性病变组织中的表达，并分析其与鼻咽癌患者临床病理特征的关系。采用定量RT-PCR、免疫印迹和荧光染色方法，对不同分化阶段的鼻咽癌细胞系和永生化鼻咽上皮NP-69细胞中UBEC 2的表达谱进行了评价。结果免疫组化结果显示UBE 2C蛋白在鼻咽癌组织中的表达水平明显高于鼻咽良性病变组织（P <0.0 0 1），而在正常鼻咽组织中的表达水平明显低于鼻咽良性病变组织（P<0.0 0 1）。UBE 2C蛋白的高表达与肿瘤大小（P=0.017）、淋巴结转移（P=0.016）和远处转移（P=0.015）呈正相关，而UBE 2C蛋白的表达水平与鼻咽癌细胞的分化程度呈负相关，而在NP-69细胞中呈低表达。UBE 2C基因的敲除可使鼻咽癌细胞周期阻滞于S期和G2/M期，并使低分化的CNE 2 Z鼻咽癌细胞和未分化的C666-1细胞的增殖能力下降，而在高分化的CNE 1和永生化的NP-69细胞中则无此现象。并可能是NPC进展的潜在标志物。
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,UBE2Cwas 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 vitroexperiments 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 ofUBE2Cled 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.
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