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

Research Paper

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

Xuanyu Zhang1,2*, Runzhou Zhuang1,2*, Qianwei Ye1,2, Jianyong Zhuo1,2, Kangchen Chen1,2, Di Lu1,2, Xuyong Wei1,2, Haiyang Xie1,2, Xiao Xu1,2✉, Shusen Zheng1,2✉

1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou 310003,China
2. NHFPC Key Laboratory of Combined Multi-organ Transplantation, Zhejiang Province, Hangzhou 310003, China
*Xuanyu Zhang and Runzhou Zhang contributed equally to this work.

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Zhang X, Zhuang R, Ye Q, Zhuo J, Chen K, Lu D, Wei X, Xie H, Xu X, Zheng S. High Expression of Human AugminComplex Submit 3 Indicates Poor Prognosis and Associates with Tumor Progression in Hepatocellular Carcinoma. J Cancer 2019; 10(6):1434-1443. doi:10.7150/jca.28317. Available from http://www.jcancer.org/v10p1434.htm

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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 (p=0.025) and tumor multiplicity (p=0.004). 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.

Keywords: Haus3, G2/M arrest, HCC, PLK1, Cdk1/cyclin B1 complex