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Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells

Biotechnology Letters volume 35, pages 29–37 (2013)Cite this article

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor and hepatitis B virus X protein (HBx) plays a crucial role in its pathogenesis. The Notch1 signaling pathway is involved in various malignant tumors including liver cancers and down-regulation of Notch-1 may exert anti-tumor effects. Here, we demonstrate that inhibition of Notch1 by plasmid-based shRNA suppresses growth of human hepatic cells transfected with HBx through G0/G1 cell cycle arrest and apoptosis inhibition, possibly linked to the promoted expression of cyclin-dependent kinase inhibitor, P16, and decreased expression of apoptosis inhibitor, Bcl-2. The anti-proliferative and pro-apoptotic effects of Notch1 shRNA in HBx-transformed L02 cell may be partly mediated by down-regulation of nuclear factor-kappaB (NF-κB) binding activities, demonstrating possible cross-talk between Notch-1 and NF-κB signaling pathways. The oncogene HBx may therefore induce malignant transformation of human hepatic cells via Notch1 pathway, indicating that Notch1 plays a crucial role in HBx-related liver cancer and could be an effective therapeutic target for HCC.

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Acknowledgments

This work was supported by the National Science Foundation of China, No. 30971352.

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No conflicts of interest are involved in this manuscript.

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Affiliations

  1. Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang-Street 1095, Wuhan, 430030, People’s Republic of China

    Fan Wang, Xiumei Xia, Jinling Wang, Qian Sun, Jin Luo & Bin Cheng

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  1. Fan Wang
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  2. Xiumei Xia
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  3. Jinling Wang
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  4. Qian Sun
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  5. Jin Luo
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  6. Bin Cheng
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Correspondence to Bin Cheng.

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Wang, F., Xia, X., Wang, J. et al. Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells. Biotechnol Lett 35, 29–37 (2013). https://doi.org/10.1007/s10529-012-1048-7

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  • DOI: https://doi.org/10.1007/s10529-012-1048-7

Keywords

  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Inhibitor Bcl-2
  • Inhibitor P16
  • Notch
  • shRNA