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Tumor Biology

, Volume 36, Issue 4, pp 2569–2581 | Cite as

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

  • Baoying Hu
  • Dawei Jiang
  • Yuyan Chen
  • Lixian Wei
  • Shusen Zhang
  • Fengbo Zhao
  • Runzhou Ni
  • Cuihua Lu
  • Chunhua Wan
Research Article

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.

Keywords

Hepatocellular carcinoma CHMP4B Cell proliferation Prognosis Doxorubicin resistance 

Notes

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).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Baoying Hu
    • 1
  • Dawei Jiang
    • 2
  • Yuyan Chen
    • 3
  • Lixian Wei
    • 2
  • Shusen Zhang
    • 2
  • Fengbo Zhao
    • 1
  • Runzhou Ni
    • 2
  • Cuihua Lu
    • 2
  • Chunhua Wan
    • 4
  1. 1.Basic Medical Research Centre, Medical CollegeNantong UniversityNantongChina
  2. 2.Department of Digestion, Affiliated Hospital of Nantong UniversityNantong UniversityNantongChina
  3. 3.Class 5, Grade 13, Clinical Medicine, Medical CollegeNantong UniversityNantongChina
  4. 4.Jiangsu Province Key Laboratory for Inflammation and Molecular Drug TargetNantong UniversityNantongChina

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