Hepatitis B virus core protein promotes the expression of neuraminidase 1 to facilitate hepatocarcinogenesis

Abstract

Neuraminidase 1 (NEU1) has been reported to be associated with hepatocellular carcinoma (HCC). However, the function and associated molecular mechanisms of NEU1 in hepatitis B virus (HBV)-related HCC have not been well investigated. In the present study, the expression of NEU1 mediated by HBV and HBV core protein (HBc) was measured in hepatoma cells. The expression of NEU1 protein was detected via immunohistochemical analysis in HBV-associated HCC tissues. The role of NEU1 in the activation of signaling pathways and epithelial-mesenchymal transition (EMT) and the proliferation and migration of hepatoma cells mediated by HBc was assessed. We found that NEU1 was upregulated in HBV-positive hepatoma cells and HBV-related HCC tissues. HBV promoted NEU1 expression at the mRNA and protein level via HBc in hepatoma cells. Mechanistically, HBc was able to enhance the activity of the NEU1 promoter through NF-κB binding sites. In addition, through the increase in NEU1 expression, HBc contributed to activation of downstream signaling pathways and EMT in hepatoma cells. Moreover, NEU1 facilitated the proliferation and migration of hepatoma cells mediated by HBc. Taken together, our findings provide novel insight into the molecular mechanism underlying the oncogenesis mediated by HBc and demonstrate that NEU1 plays a vital role in HBc-mediated functional abnormality in HCC. Thus, NEU1 may serve as a potential therapeutic target in HBV-associated HCC.

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Fig. 1: The role of HBc in NEU1 expression in HBV-related hepatoma cells.
Fig. 2: The effect of the NF-κB pathway in activation of the NEU1 promoter mediated by HBc in hepatoma cells.
Fig. 3: The role of NEU1 inhibition via shRNA in intracellular signaling pathways and EMT in HBc-positive hepatoma cells.
Fig. 4: The effect of NEU1 inhibition by OP on intracellular signaling pathways and EMT in HBc-positive hepatoma cells.
Fig. 5: The role of NEU1 in the proliferation of hepatoma cells induced by HBc.
Fig. 6: The effect of NEU1 on the migration of hepatoma cells mediated by HBc.

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Acknowledgements

The work was supported by a project funded by Jiangsu Health and Family Planning Commission (Z2018017), National Natural Science Foundation of China (81702053), Natural Science Foundation of Jiangsu Province (BK20170263), the China Postdoctoral Science Foundation funded Project (2016M591925), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Scientific Research Foundation for the Talents of Xuzhou Medical University (D2016011), and the Jiangsu Planned Projects for Postdoctoral Research Funds (1601190C).

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Correspondence to Hongjuan You or Renxian Tang.

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Kong, F., Li, N., Tu, T. et al. Hepatitis B virus core protein promotes the expression of neuraminidase 1 to facilitate hepatocarcinogenesis. Lab Invest (2020). https://doi.org/10.1038/s41374-020-0465-9

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