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Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma

  • Authors:
    • Chengzhi Xie
    • Zhenhui Lu
    • Guoxing Liu
    • Yu Fang
    • Jiefeng Liu
    • Zhao Huang
    • Fusheng Wang
    • Xiaolong Wu
    • Xiaohua Lei
    • Xiaocheng Li
    • Yueming Zhang
    • Zecheng Hu
    • Ke Qian
    • Jixiong Hu
    • Shengfu Huang
    • Dewu Zhong
    • Xundi Xu
  • View Affiliations / Copyright

    Affiliations: Division of Hepatobiliary‑Pancreatic Surgery, Department of Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China
    Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 653-660
    |
    Published online on: July 9, 2015
       https://doi.org/10.3892/ijmm.2015.2279
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Abstract

Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription‑quantitative polymerase chain reaction and immunohistochemical examination; its association with the prognosis of HCC patients was analyzed. In addition, the effects of Numb deletion on proliferation of HCC cells and its relevant molecules were evaluated in Huh7 and HepG2 cells. Numb overexpression was observed in 62% of adjacent non‑tumor tissues and 46% of tumor tissues. Overexpression of Numb in HCC was associated with histological grade, portal vein invasion and the number of tumors (P=0.001, 0.022 and 0.034 respectively). Multivariate analysis revealed that Numb expression was an independent prognostic indicator of HCC patients. Methylation of the Numb promoter contributed to hepatocarcinogenesis. In vitro assays demonstrated that Numb silencing resulted in inhibition of cell proliferation, induction of apoptosis, downregulation of cyclin‑dependent protein kinase 4 (CDK4) and S‑phase kinase‑associated protein 2 (SKP2), and upregulation of Bcl‑2 homologous antagonist/killer (BAK) and cyclin‑dependent kinase inhibitor 1 (p21). The present study suggests that downregulation of Numb inhibits colony formation and cell proliferation, induces apoptosis of HCC cells and independently predicts the poor prognosis of HCC patients. Thus, Numb has a potential role in the development and progression of HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Xie C, Lu Z, Liu G, Fang Y, Liu J, Huang Z, Wang F, Wu X, Lei X, Li X, Li X, et al: Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma. Int J Mol Med 36: 653-660, 2015.
APA
Xie, C., Lu, Z., Liu, G., Fang, Y., Liu, J., Huang, Z. ... Xu, X. (2015). Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma. International Journal of Molecular Medicine, 36, 653-660. https://doi.org/10.3892/ijmm.2015.2279
MLA
Xie, C., Lu, Z., Liu, G., Fang, Y., Liu, J., Huang, Z., Wang, F., Wu, X., Lei, X., Li, X., Zhang, Y., Hu, Z., Qian, K., Hu, J., Huang, S., Zhong, D., Xu, X."Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma". International Journal of Molecular Medicine 36.3 (2015): 653-660.
Chicago
Xie, C., Lu, Z., Liu, G., Fang, Y., Liu, J., Huang, Z., Wang, F., Wu, X., Lei, X., Li, X., Zhang, Y., Hu, Z., Qian, K., Hu, J., Huang, S., Zhong, D., Xu, X."Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma". International Journal of Molecular Medicine 36, no. 3 (2015): 653-660. https://doi.org/10.3892/ijmm.2015.2279
Copy and paste a formatted citation
x
Spandidos Publications style
Xie C, Lu Z, Liu G, Fang Y, Liu J, Huang Z, Wang F, Wu X, Lei X, Li X, Li X, et al: Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma. Int J Mol Med 36: 653-660, 2015.
APA
Xie, C., Lu, Z., Liu, G., Fang, Y., Liu, J., Huang, Z. ... Xu, X. (2015). Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma. International Journal of Molecular Medicine, 36, 653-660. https://doi.org/10.3892/ijmm.2015.2279
MLA
Xie, C., Lu, Z., Liu, G., Fang, Y., Liu, J., Huang, Z., Wang, F., Wu, X., Lei, X., Li, X., Zhang, Y., Hu, Z., Qian, K., Hu, J., Huang, S., Zhong, D., Xu, X."Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma". International Journal of Molecular Medicine 36.3 (2015): 653-660.
Chicago
Xie, C., Lu, Z., Liu, G., Fang, Y., Liu, J., Huang, Z., Wang, F., Wu, X., Lei, X., Li, X., Zhang, Y., Hu, Z., Qian, K., Hu, J., Huang, S., Zhong, D., Xu, X."Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma". International Journal of Molecular Medicine 36, no. 3 (2015): 653-660. https://doi.org/10.3892/ijmm.2015.2279
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