1. Viral-human chimeric transcript predisposes risk to liver cancer development and progression
- Author
-
Ka Fai To, Arthur K.K. Ching, Anthony W.H. Chan, Tingting Sun, Mian He, Ngai Na Co, Henry Lik-Yuen Chan, Nathalie Wong, Paul B.S. Lai, Chi-Chiu Lau, Jing-Woei Li, Joanna H.M. Tong, Alissa M. Wong, Ting-Fung Chan, Raymond W.M. Lung, and Pik-Shan Li
- Subjects
Transcriptional Activation ,Cancer Research ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Epithelial-Mesenchymal Transition ,Transcription, Genetic ,viruses ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Mice, Transgenic ,Biology ,Mice ,Transcription (biology) ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Diethylnitrosamine ,Viral Regulatory and Accessory Proteins ,Promoter Regions, Genetic ,Gene ,Wnt Signaling Pathway ,beta Catenin ,Base Sequence ,Gene Expression Profiling ,Liver Neoplasms ,Wnt signaling pathway ,RNA ,Cell Biology ,Sequence Analysis, DNA ,medicine.disease ,Virology ,Long non-coding RNA ,digestive system diseases ,Gene expression profiling ,DNA-Binding Proteins ,Wnt Proteins ,Fusion transcript ,Oncology ,Cancer research ,Trans-Activators ,RNA, Long Noncoding ,Liver cancer ,Transcriptome ,Viral Fusion Proteins - Abstract
SummaryThe mutagenic effect of hepatitis B (HBV) integration in predisposing risk to hepatocellular carcinoma (HCC) remains elusive. In this study, we performed transcriptome sequencing of HBV-positive HCC cell lines and showed transcription of viral-human gene fusions from the site of genome integrations. We discovered tumor-promoting properties of a chimeric HBx-LINE1 that, intriguingly, functions as a hybrid RNA. HBx-LINE1 can be detected in 23.3% of HBV-associated HCC tumors and correlates with poorer patient survival. HBx-LINE1 transgenic mice showed heightened susceptibility to diethylnitrosamine-induced tumor formation. We further show that HBx-LINE1 expression affects β-catenin transactivity, which underlines a role in activating Wnt signaling. Thus, this study identifies a viral-human chimeric fusion transcript that functions like a long noncoding RNA to promote HCC.
- Published
- 2013