Hepatitis B virus X promotes hepatocellular carcinoma development via nuclear protein 1 pathway

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Title
Hepatitis B virus X promotes hepatocellular carcinoma development via nuclear protein 1 pathway
Author(s)
Yesol Bak; Hye-Jun Shin; In Seon Bak; D Y Yoon; Dae Yeul Yu
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 466, no. 4, pp. 676-681
Publication Year
2015
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies and chronic hepatitis B virus (HBV) infection is a major risk factor for HCC. Hepatitis B virus X (HBx) protein relates to trigger oncogenesis. HBx has oncogenic properties with a hyperproliferative response to HCC. Nuclear protein 1 (NUPR1) is a stress-response protein, frequently upregulated in several cancers. Recent data revealed that NUPR1 is involved in tumor progression, but its function in HCC is not revealed yet. Here we report HBx can induce NUPR1 in patients, mice, and HCC cell lines. In an HBx transgenic mouse model, we found that HBx overexpression upregulates NUPR1 expression consistently with tumor progression. Further, in cultured HBV positive cells, HBx knockdown induces downregulation of NUPR1. Smad4 is a representative transcription factor, regulated by HBx, and we showed that HBx upregulates NUPR1 by Smad4 dependent way. We found that NUPR1 can inhibit cell death and induce vasculogenic mimicry in HCC cell lines. Moreover, NUPR1 silencing in HepG2-HBx showed reduced cell motility. These results suggest that HBx can modulate NUPR1 expression through the Smad4 pathway and NUPR1 has a role in hepatocellular carcinoma progression.
Keyword
Cell proliferationHepatitis B virus XHepatocellular carcinomaMigrationNUPR1Vasculogenic mimicry
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2015.09.082
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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