Oncogenic Signaling Induced by HCV Infection.
Oncogenic Signaling Induced by HCV Infection.
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DOI：
10.3390/v10100538
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发表时间：
2018-10-02
期刊：
影响因子：
--
通讯作者：
Lupberger J
中科院分区：
文献类型：
--
作者：
Virzì A;Roca Suarez AA;Baumert TF;Lupberger J
肝脏经常暴露于毒素，代谢物和氧化应激，这可能会挑战器官功能和基因组稳定性。因此，肝再生是一个高度调节的过程，涉及几个连续的信号事件。因此，肝细胞中的单个致癌突变不一定导致癌症，并且肝细胞癌（HCC）的遗传谱是高度异质性的，这并不奇怪。丙型肝炎病毒（HCV）的长期感染通过病毒蛋白表达、持续性肝脏炎症、氧化应激和慢性失调信号传导事件的组合创造了致癌环境，这些事件累积为遗传稳定性的临界点。尽管新型直接作用抗病毒药物（DAA）治疗有效地根除了HCV，但在晚期肝病患者中，相关的HCC风险不能通过病毒治愈完全消除。这表明，HCV可能持续解除病毒治愈后的信号通路，从而继续扰乱癌症相关基因的功能。在这篇综述中，我们总结了目前的知识致癌信号通路脱轨的慢性HCV感染。这不仅有助于了解肝癌发生的机制，而且还将突出潜在的化学预防策略，以帮助具有发展HCC高风险特征的患者。
The liver is frequently exposed to toxins, metabolites, and oxidative stress, which can challenge organ function and genomic stability. Liver regeneration is therefore a highly regulated process involving several sequential signaling events. It is thus not surprising that individual oncogenic mutations in hepatocytes do not necessarily lead to cancer and that the genetic profiles of hepatocellular carcinomas (HCCs) are highly heterogeneous. Long-term infection with hepatitis C virus (HCV) creates an oncogenic environment by a combination of viral protein expression, persistent liver inflammation, oxidative stress, and chronically deregulated signaling events that cumulate as a tipping point for genetic stability. Although novel direct-acting antivirals (DAA)-based treatments efficiently eradicate HCV, the associated HCC risk cannot be fully eliminated by viral cure in patients with advanced liver disease. This suggests that HCV may persistently deregulate signaling pathways beyond viral cure and thereby continue to perturb cancer-relevant gene function. In this review, we summarize the current knowledge about oncogenic signaling pathways derailed by chronic HCV infection. This will not only help to understand the mechanisms of hepatocarcinogenesis but will also highlight potential chemopreventive strategies to help patients with a high-risk profile of developing HCC.
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影响因子：
5.9
作者：
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通讯作者：
Zeisel, Mirjam B.
影响因子：
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作者：
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11.2
作者：
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DOI：
10.1073/pnas.87.5.1973
发表时间：
1990-03-01
影响因子：
11.1
作者：
BRESSAC, B;GALVIN, KM;OZTURK, M
通讯作者：
OZTURK, M