Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis?
Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis?
复制标题
烟草使用会促进 HCV 诱导的 miR-122 劫持和肝癌发生吗？
DOI：
10.1016/j.mehy.2012.11.009
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发表时间：
2013-02-01
影响因子：
4.7
通讯作者：
Taylor, Ethan Will
中科院分区：
文献类型：
--
作者：
Zhao, Lijun;Li, Farong;Taylor, Ethan Will
慢性丙型肝炎病毒（HCV）感染是肝细胞癌（HCC）的公认危险因素。作为一个共同的风险因素，烟草使用在HCV驱动的致癌作用和相关的潜在机制仍不清楚。关于HCV复制的最新发现表明，HCV RNA通过形成Ago 2-HCV-miR-122复合物劫持细胞miRNA-122，该复合物稳定HCV基因组并增强HCV复制。我们以前的工作已经证明，烟草烟雾提取物（TSE）是一种有效的HIV复制激活剂，通过TSE介导的病毒保护氧化应激和激活一组基因，可以促进病毒复制。由于HCV与HIV一样，是一种包膜病毒，对脂质过氧化反应同样敏感，并且已知TSE上调基因之一DDX 3解旋酶可促进HCV复制，因此我们假设（1）烟草使用可类似地增强HCV活力和复制，并通过上调DDX 3促进HCC进展，和（2）通过与作为竞争性内源RNA（ceRNA）的miR-122竞争结合，HCV复制可以释放miR-122的直接靶点，致癌基因细胞周期蛋白G1（CCNG 1）;此外，同时使用烟草可以通过HCV上调协同增强这种竞争效应。我们的假设可能为更好地理解HCV驱动的HCC的致癌作用以及烟草作为辅助因子的潜在作用奠定基础。破坏HCVceRNA效应可能为设计抗HCV/HCC药物提供新的策略。(c)2012爱思唯尔有限公司保留所有权利。
Chronic hepatitis C virus (HCV) infection is a well-recognized risk factor for hepatocellular carcinoma (HCC). As a co-risk factor, the role of tobacco use in HCV-driven carcinogenesis and relevant underlying mechanisms remain largely unclear. The latest discoveries about HCV replication have shown that HCV RNA hijacks cellular miRNA-122 by forming an Ago2-HCV-miR-122 complex that stabilizes the HCV genome and enhances HCV replication. Our previous work has demonstrated that aqueous tobacco smoke extract (TSE) is a potent activator of HIV replication via TSE-mediated viral protection from oxidative stress and activation of a set of genes that can promote viral replication. Since HCV is, like HIV, an enveloped virus that should be equally susceptible to lipid peroxidation, and since one of the TSE-upregulated genes, the DDX3 helicase, is known to facilitate HCV replication, we hypothesize that (1) tobacco use can similarly enhance HCV viability and replication, and promote HCC progression by up-regulation of DDX3, and (2) by competing for binding with miR-122 as a competing endogenous RNA (ceRNA), HCV replication can liberate miR-122's direct target, oncogenic gene cyclin G1 (CCNG1); furthermore, simultaneous tobacco use can synergistically enhance this competing effect via HCV upregulation. Our hypotheses may lay a foundation for better understanding of carcinogenesis in HCV-driven HCC and the potential role of tobacco as a cofactor. Disrupting the HCV ceRNA effect may provide a new strategy for designing anti HCV/HCC drugs. (c) 2012 Elsevier Ltd. All rights reserved.