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泛素结合酶E2Q1(UBE2Q1)表达上调与人类肝细胞癌中细胞增殖增强及预后不良相关。

Upregulated expression of ubiquitin-conjugating enzyme E2Q1 (UBE2Q1) is associated with enhanced cell proliferation and poor prognosis in human hapatocellular carcinoma.

作者信息

Chang Renan, Wei Lixian, Lu Yuhua, Cui Xiaopeng, Lu Cuihua, Liu Luoliang, Jiang Dawei, Xiong YiCheng, Wang Gang, Wan Chunhua, Qian Haixin

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

出版信息

J Mol Histol. 2015 Feb;46(1):45-56. doi: 10.1007/s10735-014-9596-x. Epub 2014 Oct 14.

DOI:10.1007/s10735-014-9596-x
PMID:25311764
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Ubiquitin-proteasome system has been shown to play a pivotal role in the pathophysiology of HCC and other malignancies. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and may be involved in the regulation of cancer-related proteins. In this study, we investigated the expression pattern of UBE2Q1 in HCC cell lines and human HCC specimens, and its potential clinical and biological significance in HCC. Western blot and immunohistochemical analyses revealed that UBE2Q1 was significantly upregulated in HCC tumorous tissues compared with the adjacent noncancerous ones. Next, univariate and multivariate survival analyses were performed to determine the prognostic significance of UBE2Q1 in HCC. The results showed that upregulated expression of UBE2Q1 was positively correlated with high histological grades of HCC and predicted poor prognosis. In addition, the expression of UBE2Q1 was progressively increased in serum-refed HCC cells. UBE2Q1 depletion by small interfering RNA inhibited cell proliferation and led to G1 phase arrest in HepG2 and BEL-7404 cells. Furthermore, we showed that cells transfected with UBE2Q1-targeting siRNA resulted in significant increase in the levels of p53, p21 in HepG2 and BEL-7404 cells. These data imply that UBE2Q1 is upregulated in liver cancer cell lines and tumorous samples and may play a role in the development of HCC.

摘要

肝细胞癌(HCC)是全球第五大常见癌症。泛素-蛋白酶体系统已被证明在HCC及其他恶性肿瘤的病理生理学中起关键作用。UBE2Q1是一种假定的E2泛素结合酶,可能参与癌症相关蛋白的调控。在本研究中,我们调查了UBE2Q1在HCC细胞系和人类HCC标本中的表达模式,及其在HCC中的潜在临床和生物学意义。蛋白质印迹法和免疫组织化学分析显示,与相邻的非癌组织相比,UBE2Q1在HCC肿瘤组织中显著上调。接下来,进行单因素和多因素生存分析以确定UBE2Q1在HCC中的预后意义。结果表明,UBE2Q1的上调表达与HCC的高组织学分级呈正相关,并预示预后不良。此外,在血清再喂养的HCC细胞中,UBE2Q1的表达逐渐增加。通过小干扰RNA敲低UBE2Q1可抑制HepG2和BEL-7404细胞的增殖并导致G1期阻滞。此外,我们发现用靶向UBE2Q1的siRNA转染细胞会导致HepG2和BEL-7404细胞中p53、p21水平显著升高。这些数据表明,UBE2Q1在肝癌细胞系和肿瘤样本中上调,可能在HCC的发生发展中起作用。

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本文引用的文献

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Cadmium Impairs p53 Activity in HepG2 Cells.镉损害HepG2细胞中的p53活性。
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Overexpression of UBE2M through Wnt/β-Catenin signaling is associated with poor prognosis and chemotherapy resistance in colorectal cancer.通过Wnt/β-连环蛋白信号通路导致的UBE2M过表达与结直肠癌的不良预后和化疗耐药相关。
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