Hepatitis B virus (HBV) is thought to drive hepatocellular carcinoma (HCC) development through viral insertion into the host genome, but the mechanism is not fully understood. Now, Nathalie Wong, Ting-Fung Chan and colleagues report the identification of viral-human gene fusions and a recurrent chimeric transcript with oncogenic functions (Cancer Cell 25, 335–349, 2014). The authors performed transcriptome sequencing of six HBV-positive HCC cell lines and identified chimeric viral-human transcripts in four of the lines. They found virus-driven expression of a long interspersed nuclear element (LINE1) repetitive sequence generating a chimeric HBx-LINE1 transcript, which was expressed in about 23% of HBV-associated HCC tumors. Knockdown of HBx-LINE1b reduced the migratory and invasive properties of HCC cells, decreased expression of markers of the epithelial-to-mesenchymal transition and reduced the transactivation activity of β-catenin, whereas transgene-driven expression of HBx-LINE1b promoted cell migration and invasion. Only the full-length HBx-LINE1 transcript had functional effects, suggesting that the transcript functions as a long noncoding RNA. Finally, the authors generated HBx-LINE1 transgenic mice, which were found to be more susceptible to diethylnitrosamine-induced HCC formation.
Rights and permissions
About this article
Cite this article
Niemitz, E. Oncogenic chimeric transcript. Nat Genet 46, 423 (2014). https://doi.org/10.1038/ng.2976
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng.2976