4.6 Article

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

期刊

JOURNAL OF CANCER
卷 10, 期 6, 页码 1434-1443

出版社

IVYSPRING INT PUBL
DOI: 10.7150/jca.28317

关键词

Haus3; G2/M arrest; HCC; PLK1; Cdk1/cyclin B1 complex

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资金

  1. National ST Major Project [2017ZX10203205]
  2. Projects of Medical and Health Technology Program in Zhejiang province [2015KYB062]
  3. Natural Science Foundation of Zhejiang Province [LQ19H160030]
  4. Medical Science and Technology Project of Zhejiang Province [2016146968]

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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 that expression of Haus3 was an independent prognostic factor for overall survival of HCC patients. 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 ofa-tubulin and gamma-tubulin. In summary, Haus3 plays a vital role in regulating the activity of 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.

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