Department of Pathology & Pathophysiology, School of Basic Medicine Science, Guangdong Medical College, Zhanjiang 524023, People's Republic of China.
BMC Cancer. 2013 Apr 15;13:192. doi: 10.1186/1471-2407-13-192.
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.
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.
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.
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.
泛素结合酶 2C（UBE2C）的过表达已在多种人类癌症中被检测到，并且与肿瘤恶性程度相关。然而，UBE2C 在人类鼻咽癌（NPC）中的作用尚不清楚。在这项研究中，我们研究了异常 UBE2C 表达在人类 NPC 进展中的作用。
通过免疫组织化学分析检测 NPC 和良性鼻咽组织的临床样本中 UBE2C 蛋白的表达，并分析 UBE2C 表达与患者临床病理特征的关系。使用定量 RT-PCR、Western blot 和荧光染色评估代表 NPC 不同分化阶段的细胞系和永生化鼻咽上皮 NP-69 细胞中 UBEC2 的表达谱。此外，在这些细胞系中使用 RNA 干扰敲低 UBE2C，并研究增殖和细胞周期分布。
免疫组织化学分析显示，UBE2C 蛋白在 NPC 组织中的表达水平高于良性鼻咽组织（P<0.001）。此外，UBE2C 蛋白高表达与 NPC 患者的肿瘤大小（P=0.017）、淋巴结转移（P=0.016）和远处转移（P=0.015）呈正相关。体外实验表明，UBE2C 表达水平与 NPC 细胞系的分化程度呈负相关，而 UBE2C 在 NP-69 细胞中的表达水平较低。UBE2C 的敲低导致细胞周期 S 和 G2/M 期显著停滞，并且在低分化 CNE2Z NPC 细胞和未分化 C666-1 细胞中观察到细胞增殖减少，但在高分化 CNE1 和永生化 NP-69 细胞中则没有。
我们的研究结果表明，人类 NPC 中 UBE2C 的高表达与肿瘤恶性程度密切相关，可能是 NPC 进展的潜在标志物。
