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人类Augmin复合物亚基3的高表达预示肝细胞癌预后不良并与肿瘤进展相关。

High Expression of Human AugminComplex Submit 3 Indicates Poor Prognosis and Associates with Tumor Progression in Hepatocellular Carcinoma.

作者信息

Zhang Xuanyu, Zhuang Runzhou, Ye Qianwei, Zhuo Jianyong, Chen Kangchen, Lu Di, Wei Xuyong, Xie Haiyang, Xu Xiao, Zheng Shusen

机构信息

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou 310003,China.

NHFPC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, Hangzhou 310003, China.

出版信息

J Cancer. 2019 Feb 23;10(6):1434-1443. doi: 10.7150/jca.28317. eCollection 2019.

Abstract

The function of human augmin complex unit 3(Haus3), a component of the HAU augmin-like complex, in various cancers is not clear. This study aims to elucidate the clinical significance and the role of Haus3 in tumor progression of hepatocellular carcinoma (HCC). We analyzed the expression of Haus3 in 50 HCC patients from The Cancer Genome Atlas and 137 HCC patients in our hospital. Compared with adjacent normal tissue, Haus3 expression assessed by immunohistochemical staining was dramatically increased in tumor tissues. A high level of Haus3 expression was significantly correlated with large tumor size () and tumor multiplicity (). Univariate and multivariate survival analysis showed thatexpression of Haus3 was an independent prognostic factor for overall survival ofHCCpatients. Western blot analysis showed that Haus3 regulated the phosphorylation of PLK1-T210 and activity of the Cdk1/cyclin B1 complex, indicating that Haus3 disrupted G2/M phase arrest. In immunofluorescence studies, expression of Haus3 correlated with the level ofα-tubulin and γ-tubulin. In summary, Haus3 plays a vital role in regulatingtheactivityof PLK2-T210 and Cdk1/cyclin B1 complex in G2/M phasetransition and the expression of tubulins to ensure normal mitotic progression. Our data suggest that Haus3 might be a promising prognostic biomarker and molecular target of HCC.

摘要

人Augmin复合体亚基3(Haus3)作为HAU类Augmin复合体的一个组成部分,在多种癌症中的作用尚不清楚。本研究旨在阐明Haus3在肝细胞癌(HCC)肿瘤进展中的临床意义及作用。我们分析了来自癌症基因组图谱(The Cancer Genome Atlas)的50例HCC患者以及我院137例HCC患者中Haus3的表达情况。与癌旁正常组织相比,通过免疫组织化学染色评估发现肿瘤组织中Haus3的表达显著增加。高水平的Haus3表达与肿瘤大尺寸()和肿瘤多灶性()显著相关。单因素和多因素生存分析表明,Haus3的表达是HCC患者总生存的独立预后因素。蛋白质免疫印迹分析表明,Haus3调节PLK1 - T210的磷酸化以及Cdk1/细胞周期蛋白B1复合体的活性,这表明Haus3破坏了G2/M期阻滞。在免疫荧光研究中,Haus3的表达与α - 微管蛋白和γ - 微管蛋白的水平相关。总之,Haus3在G2/M期转换过程中调节PLK2 - T210和Cdk1/细胞周期蛋白B1复合体的活性以及微管蛋白的表达,以确保正常的有丝分裂进程,发挥着至关重要的作用。我们的数据表明,Haus3可能是一种有前景的HCC预后生物标志物和分子靶点。 (注:原文中括号部分内容缺失,翻译时保留原文格式)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9ea/6485217/f1125f3d7a55/jcav10p1434g001.jpg

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