Viral-human chimeric transcript predisposes risk to liver cancer development and progression

Autor: 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, Pik-Shan Li
Rok vydání: 2013
Předmět:
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
Zdroj: Cancer cell. 25(3)
ISSN: 1878-3686
Popis: 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.
Databáze: OpenAIRE
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