Abstract
The involvement of the hepatitis B virus X (HBx) protein in epigenetic modifications during hepatocarcinogenesis has been previously characterized. Long noncoding RNAs (lncRNAs), a kind of epigenetic regulator molecules, have also been shown to play crucial roles in HBx-related hepatocellular carcinoma (HCC). In this study, we analyzed the key transcription factors of aberrantly expressed lncRNAs in the livers of HBx transgenic mice by bioinformatics prediction, and found that ecotropic viral integration site 1 (Evi1) was a potential main transcription regulator. Further investigation showed that EVI1 was positively correlated to HBx expression and was frequently up-regulated in HBV-related HCC tissues. The forced expression of HBx in liver cell lines resulted in a significant increase of the expression of EVI1. Furthermore, suppression of EVI1 expression decreased the proliferation of HCC cells overexpressing HBx in vitro and in vivo.Conclusion: Our findings suggest that EVI1 is frequently up-regulated and regulates a cluster of lncRNAs in HBV-related hepatocellular carcinoma (HCC). These findings highlight a novel mechanism for HBx-induced hepatocarcinogenesis through transcription factor EVI1 and its target lncRNAs, and provide a potential new approach to predict the functions of lncRNAs.
Highlights
Hepatocellular carcinoma (HCC) is a prevalent cancer in the world, especially in Asia and Africa
Our findings suggest that ecotropic viral integration site 1 (EVI1) is frequently up-regulated and regulates a cluster of long non-coding RNA (lncRNA) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)
These findings highlight a novel mechanism for hepatitis B virus X protein (HBx)-induced hepatocarcinogenesis through transcription factor EVI1 and its target lncRNAs, and provide a potential new approach to predict the functions of lncRNAs
Summary
Hepatocellular carcinoma (HCC) is a prevalent cancer in the world, especially in Asia and Africa. Chronic hepatitis B virus (HBV) infection is responsible for the great majority of HCC in these areas, which can result in end-stage liver disease, including liver cirrhosis and HCC. Recent studies have demonstrated that genetic alterations alone cannot account for the complexity of human HBV-related hepatocarcinogenesis, but that epigenetic changes, such as DNA methylation [2], histone modifications [3], and noncoding RNA expression [4, 5], are involved in this process. The hepatitis B virus X protein (HBx) has been implicated in HBV-related hepatocarcinogenesis and considered to be oncogenic [6, 7]. There are epigenetic modifications, as much as genetic regulation involved in HBx-induced hepatocarcinogenesis [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
