Viral-Human Chimeric Transcript Predisposes Risk to Liver Cancer Development and Progression
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AbstractThe 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 beta-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.
All Author(s) ListLau CC, Sun TT, Ching AKK, He M, Li JW, Wong AM, Co NN, Chan AWH, Li PS, Lung RWM, Tong JHM, Lai PBS, Chan HLY, To KF, Chan TF, Wong N
Journal nameCancer Cell
Volume Number25
Issue Number3
PublisherElsevier (Cell Press)
Pages335 - 349
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesCell Biology; CELL BIOLOGY; Oncology; ONCOLOGY

Last updated on 2021-18-09 at 23:59