Viral-Human Chimeric Transcript Predisposes Risk to Liver Cancer Development and Progression
Viral-Human Chimeric Transcript Predisposes Risk to Liver Cancer Development and Progression
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DOI：
10.1016/j.ccr.2014.01.030
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发表时间：
2014-03-17
期刊：
影响因子：
50.3
通讯作者：
Wong, Nathalie
中科院分区：
文献类型：
--
作者：
Lau, Chi-Chiu;Sun, Tingting;Wong, Nathalie
B型肝炎（HBV）整合在诱发肝细胞癌（HCC）风险中的致突变作用仍不清楚。在这项研究中，我们对HBV阳性的HCC细胞系进行了转录组测序，并显示了来自基因组整合位点的病毒-人基因融合的转录。我们发现了嵌合HBx-LINE 1的肿瘤促进特性，有趣的是，它作为一种杂交RNA发挥作用。HBx-LINE 1可在23.3%的HBV相关HCC肿瘤中检测到，并与患者生存率较差相关。HBx-LINE 1转基因小鼠对二乙基亚硝胺诱导的肿瘤形成表现出更高的易感性。我们进一步表明，HBx-LINE 1表达影响β-连环蛋白的反式作用，这强调了激活Wnt信号的作用。因此，这项研究确定了一种病毒-人嵌合融合转录本，其功能类似于长的非编码RNA，以促进HCC。
The 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.