UBE2C is involved in the functions of ECRG4 on esophageal squamous cell carcinoma
UBE2C is involved in the functions of ECRG4 on esophageal squamous cell carcinoma
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DOI：
10.1016/j.biopha.2017.12.066
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发表时间：
2018-02-01
影响因子：
7.5
通讯作者：
Shi, Zuxuan
中科院分区：
文献类型：
--
作者：
Li, Linwei;Li, Xiaoyan;Shi, Zuxuan
背景：食管癌相关基因4（ECRG4）在食管鳞状细胞癌（ESCC）中下调并抑制ESCC细胞的致瘤性。泛素结合酶 E2 (UBE2C) 是一种 E2 泛素结合酶，在包括食管鳞癌在内的多种人类癌症中表达上调。方法：分别通过实时 PCR 和蛋白质印迹分析测定 mRNA 和蛋白质表达。通过Annexin V-异硫氰酸荧光素染色和流式细胞术分析评估细胞凋亡。结果：通过分析之前EC9706细胞的定量蛋白质组学数据，我们发现UBE2C在ECRG4过表达的细胞中显着下调。蛋白质印迹分析验证了 EC9706 和 EC-18 细胞中的蛋白质组学结果。此外，Pearson相关分析显示ESCC组织中ECRG4和UBE2C的mRNA水平呈负相关。然后，我们发现核因子-kappa B (NF-kappa B) 抑制剂吡咯烷二硫代氨基甲酸酯 (PDTC) 可以抑制 NF-kappa B p65 核转位和 UBE2C 表达，而 ECRG4 沉默可部分逆转这一现象。更重要的是，敲低TE-1细胞中的UBE2C可显着抑制细胞增殖并诱导细胞凋亡，敲低ECRG4可部分逆转这种情况。结论：ECRG4通过NF-kappa B信号传导下调ESCC细胞中UBE2C的表达。 UBE2C 参与 ESCC 细胞中 ECRG4 的抗增殖和促凋亡功能。
Background: Esophageal cancerrelated gene 4 (ECRG4) is down-regulated in esophageal squamous-cell carcinoma (ESCC) and inhibits the tumorigenicity of ESCC cells. Ubiquitin conjugating enzyme E2 (UBE2C), an E2 ubiquitin-conjugating enzyme, is upregulated in numerous human cancers, including ESCC.Methods: mRNA and protein expression was determined by real-time PCR and western blotting analysis, respectively. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate staining and flow cytometry analysis.Results: By analyzing previous quantitative proteomics data on EC9706 cells, we found that UBE2C was significantly down-regulated in ECRG4 overexpressed cells. Western blotting analysis validated the proteomics results in both EC9706 and EC-18 cells. In addition, Pearson's correlation analysis demonstrated a negative correlation between the mRNA levels of ECRG4 and UBE2C in ESCC tissues. Then, we found that Nuclear Factor-kappa B (NF-kappa B) inhibitor, pyrriolidine-dithiocarbamate (PDTC), could inhibit NF-kappa B p65 nuclear translocation and UBE2C expression, which was partially reversed by ECRG4 silence. More importantly, UBE2C knockdown in TE-1 cells significantly inhibited cell proliferation and induced cell apoptosis, which was partially reversed by ECRG4 knockdown.Conclusions: ECRG4 down-regulated UBE2C expression in ESCC cells via NF-kappa B signaling. UBE2C was involved in the anti-proliferative and pro-apoptotic functions of ECRG4 in ESCC cells.