[HTML][HTML] USP16 downregulation by carboxyl-terminal truncated HBx promotes the growth of hepatocellular carcinoma cells

Y Qian, B Wang, A Ma, L Zhang, G Xu, Q Ding, T Jing… - Scientific reports, 2016 - nature.com
Y Qian, B Wang, A Ma, L Zhang, G Xu, Q Ding, T Jing, L Wu, Y Liu, Z Yang, Y Liu
Scientific reports, 2016nature.com
Hepatitis B virus (HBV) infection is a major factor that contributes to the development of
hepatocellular carcinoma (HCC). HBV X protein (HBx) has been shown to accelerate HCC
progression by promoting tumour growth and metastasis. In the clinic, carboxyl-terminal
truncated HBx (Ct-HBx) proteins are frequently present in HCC tumour tissues, but not in
non-tumorous tissues. In this study, we analysed deubiquitinase expression profiles in cells
with or without ectopic expression of the Ct-HBx proteins and observed that the expression …
Abstract
Hepatitis B virus (HBV) infection is a major factor that contributes to the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) has been shown to accelerate HCC progression by promoting tumour growth and metastasis. In the clinic, carboxyl-terminal truncated HBx (Ct-HBx) proteins are frequently present in HCC tumour tissues, but not in non-tumorous tissues. In this study, we analysed deubiquitinase expression profiles in cells with or without ectopic expression of the Ct-HBx proteins and observed that the expression of ubiquitin specific peptidase 16 (USP16) was substantially inhibited by Ct-HBx proteins. Liver tumour cells with forced down-regulation of USP16 exhibited increased capabilities for colony formation and tumour growth in vivo. In addition, USP16 inhibition promoted stem-like properties in tumour cells, as evidenced by their spheroid formation and chemo-responsiveness. Furthermore, ectopic expression of USP16 in tumour cells significantly abrogated the tumour promoting activities of the Ct-HBx proteins (HBxΔ35), leading to decreased tumour cell viability and tumour growth. In human HCCs, USP16 was frequently downregulated, and the decreased expression of USP16 was correlated with high tumour stages and poor differentiation status. Taken together, our study suggests that USP16 downregulation is a critical event in Ct-HBx-mediated promotion of HCC tumorigenicity and malignancy.
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