Links between Human LINE-1 Retrotransposons and Hepatitis Virus-Related Hepatocellular Carcinoma.
Links between Human LINE-1 Retrotransposons and Hepatitis Virus-Related Hepatocellular Carcinoma.
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DOI：
10.3389/fchem.2016.00021
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发表时间：
2016
影响因子：
5.5
通讯作者：
Honda T
中科院分区：
文献类型：
--
作者：
Honda T
肝细胞癌（HCC）约占肝癌的80%，是癌症死亡的第三大常见原因。HCC最常见的危险因素是乙型或丙型肝炎病毒感染。研究结果表明，肝炎病毒相关的HCC可能是一种LINE-1逆转录转座子（通常称为L1）活性起潜在作用的癌症。首先，肝炎病毒可以抑制宿主防御因子，而宿主防御因子也控制L1的动员。其次，近期许多研究也表明L1的低甲基化影响HCC患者的预后。第三，内源性L1逆转录被证明可以激活HCC的致癌途径。第四，在肝炎病毒相关的HCC中发现了几种与宿主或病毒基因的L1嵌合转录物。这些证据提示L1逆转录转座子与肝炎病毒相关性HCC之间存在联系。在这里，我简要总结了目前对肝炎病毒相关性HCC与L1之间关系的理解。然后，我讨论了肝炎病毒如何通过L1反转录转座子驱动HCC发展的潜在机制。对L1在肝炎病毒相关HCC中的作用的进一步了解可能为开发这种疾病的新疗法提供独特的见解。
Hepatocellular carcinoma (HCC) accounts for approximately 80% of liver cancers, the third most frequent cause of cancer mortality. The most prevalent risk factors for HCC are infections by hepatitis B or hepatitis C virus. Findings suggest that hepatitis virus-related HCC might be a cancer in which LINE-1 retrotransposon, often termed L1, activity plays a potential role. Firstly, hepatitis viruses can suppress host defense factors that also control L1 mobilization. Secondly, many recent studies also have indicated that hypomethylation of L1 affects the prognosis of HCC patients. Thirdly, endogenous L1 retrotransposition was demonstrated to activate oncogenic pathways in HCC. Fourthly, several L1 chimeric transcripts with host or viral genes are found in hepatitis virus-related HCC. Such lines of evidence suggest a linkage between L1 retrotransposons and hepatitis virus-related HCC. Here, I briefly summarize current understandings of the association between hepatitis virus-related HCC and L1. Then, I discuss potential mechanisms of how hepatitis viruses drive the development of HCC via L1 retrotransposons. An increased understanding of the contribution of L1 to hepatitis virus-related HCC may provide unique insights related to the development of novel therapeutics for this disease.