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High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma

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Tumor Biology

Abstract

Charged multivesicular body protein 4B (CHMP4B), a subunit of the endosomal sorting complex required for transport (ESCRT)-III complex, plays an important part in cytokinetic membrane abscission and the late stage of mitotic cell division. In this study, we explored the prognostic significance of CHMP4B in human hepatocellular carcinoma (HCC) and its impact on the physiology of HCC cells. Western blot and immunohistochemistrical analyses showed that CHMP4B was significantly upregulated in HCC tissues, compared with adjacent non-tumorous tissues. Meanwhile, clinicopathological analysis revealed that high CHMP4B expression was correlated with multiple clinicopathological variables, including AFP, cirrhosis, AJCC stage, Ki-67 expression, and poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that CHMP4B served as an independent prognostic factor for survival of HCC patients. Using HCC cell cultures, we found that the expression of CHMP4B was progressively upregulated after the release from serum starvation. To verify whether CHMP4B could regulate the proliferation of HCC cells, CHMP4B was knocked down through the transfection of CHMP4B-siRNA oligos. Flow cytometry and CCK-8 assays indicated that interference of CHMP4B led to cell cycle arrest and proliferative impairment of HCC cells. Additionally, depletion of CHMP4B expression could increase the sensitivity to doxorubicin in HepG2 and Huh7 cells. Taken together, our results implied that CHMP4B could be a promising prognostic biomarker as well as a potential therapeutic target of HCC.

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Acknowledgments

This study was supported, in part, by the National Natural Science Foundation of China (No. 81272708) and a grant from the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 12KJB320005).

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Authors and Affiliations

  1. Basic Medical Research Centre, Medical College, Nantong University, Nantong, 226001, China

    Baoying Hu & Fengbo Zhao

  2. Department of Digestion, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu, 226001, China

    Dawei Jiang, Lixian Wei, Shusen Zhang, Runzhou Ni & Cuihua Lu

  3. Class 5, Grade 13, Clinical Medicine, Medical College, Nantong University, Nantong, Jiangsu, 226001, China

    Yuyan Chen

  4. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China

    Chunhua Wan

Authors
  1. Baoying Hu
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  2. Dawei Jiang
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  3. Yuyan Chen
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  4. Lixian Wei
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  5. Shusen Zhang
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  7. Runzhou Ni
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  8. Cuihua Lu
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  9. Chunhua Wan
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Corresponding authors

Correspondence to Cuihua Lu or Chunhua Wan.

Additional information

Baoying Hu and Dawei Jiang contributed equally to this work.

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Hu, B., Jiang, D., Chen, Y. et al. High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma. Tumor Biol. 36, 2569–2581 (2015). https://doi.org/10.1007/s13277-014-2873-1

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  • DOI: https://doi.org/10.1007/s13277-014-2873-1

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