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http://hdl.handle.net/10397/68572
Title: | C-terminal truncated hepatitis B virus X protein regulates tumorigenicity, self-renewal and drug resistance via STAT3/Nanog signaling pathway | Authors: | Ching, RHH Sze, KMF Lau, EYT Chiu, YT Lee, JMF Ng, IOL Lee, TKW |
Issue Date: | 2017 | Source: | Oncotarget, 2017, v. 8, no. 14, p. 23507-23516 | Abstract: | Hepatitis B virus (HBV) is a major risk factor of chronic liver disease and hepatocellular carcinoma (HCC). Random integration of HBV DNA into the host genome is frequent in HCC leading to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). C-terminally truncated HBx (HBx-Delta C) has been implicated in playing a pro-oncogenic role in hepatocarcinogenesis. However, the mechanism whereby HBx-Delta C1 contributes to hepatocarcinogenesis remains unclear. In this study, we investigated the functional role of HBx-Delta C1 in regulating liver cancer stem cell (CSC) properties. Using Tet-on inducible system, we found that HBx-Delta C1 enhanced CSC properties including self-renewal, tumorigenicity, chemoresistance, migration and expression of liver CSC markers, when compared with the full-length HBx counterpart and vector control. Interestingly, HBx-Delta C1 conferred resistance in HCC cells towards sorafenib treatment through suppression of apoptotic cascade. In addition, HBx-Delta C1 upregulated a panel of stemness genes, in which Nanog was found to be among the most significant one in both trasnfected cell lines. Consistently, Nanog was upregulated in human HCC samples which had HBx-Delta C1 expression. Furthermore, the induction of CSC properties by HBx-Delta C1 was via the Stat3/Nanog pathway, as administration of Stat3 inhibitor abolished the HBx-Delta C1-induced self-renewing capacity. In conclusion, our data suggest that HBx-Delta C1 enhances liver CSCs properties through Stat3/Nanog cascade, and provide a new insight for the therapeutic intervention for HBV-related HCC. | Keywords: | Truncated HBx HCC Nanog Stat3 Stemness Hepatocellular carcinoma |
Publisher: | Impact Journals LLC | Journal: | Oncotarget | ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.15183 | Rights: | Oncotarget applies the Creative Commons Attribution 3.0 License (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/) to all works we publish (read the human-readable summary or the full license legal code). Under the CC BY, authors retain ownership of the copyright for their article, but authors allow anyone to download, reuse, reprint, modify, distribute, and/or copy articles in Oncotarget, so long as the original authors and source are cited. |
Appears in Collections: | Journal/Magazine Article |
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