Hepatitis B virus X protein accelerates the development of hepatoma.
Hepatitis B virus X protein accelerates the development of hepatoma.
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DOI：
10.7497/j.issn.2095-3941.2014.03.004
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发表时间：
2014-09
影响因子：
5.5
通讯作者：
Ye LH
中科院分区：
文献类型：
--
作者：
Zhang XD;Wang Y;Ye LH
B型肝炎病毒（HBV）的慢性感染与肝细胞癌（HCC）的发生、发展密切相关。越来越多的证据表明，HBV X蛋白（HBx蛋白）是一种多功能的调节因子，在肝癌的发生发展中起着重要的作用。然而，HBV诱导HCC的机制的信息是缺乏的。本文就HBx在HBV致肝癌中的病理作用作一综述。作为一种反式激活因子，HBx可调节活化B细胞核因子κ轻链增强子（NF-κB）和转录因子AP-2。此外，HBx可以影响调节性非编码RNA（ncRNA），包括microRNA和长ncRNA（lncRNA），例如miRNA-205和在肝癌（HULC）中分别高度上调。HBx还参与表观遗传修饰，包括甲基化和乙酰化。HBx与多种信号转导途径相互作用，如蛋白激酶B/Akt、Wnt/β-catenin、信号转导和转录激活因子以及NF-κB途径。此外，HBx通过将平衡转向细胞存活来影响细胞命运。HBx可能导致凋亡功能的丧失或通过实现转化功能直接促进肿瘤发生，从而诱导肝癌发生。此外，HBx可以通过与宿主因子的直接或间接相互作用来调节细胞凋亡和免疫应答。我们的结论是HBx加速肝癌的发展。
The chronic infection of hepatitis B virus (HBV) is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Accumulated evidence has shown that HBV X protein (HBx protein) is a multifunctional regulator with a crucial role in hepatocarcinogenesis. However, information on the mechanism by which HBV induces HCC is lacking. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator, HBx can modulate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transcription factor AP-2. Moreover, HBx can affect regulatory non-coding RNAs (ncRNAs) including microRNAs and long ncRNAs (lncRNAs), such as miRNA-205 and highly upregulated in liver cancer (HULC), respectively. HBx is also involved in epigenetic modification, including methylation and acetylation. HBx interacts with various signal-transduction pathways, such as protein kinase B/Akt, Wnt/β-catenin, signal transducer and activator of transcription, and NF-κB pathways. Moreover, HBx affects cellular fate by shifting the balance toward cell survival. HBx may lead to the loss of apoptotic functions or directly contributes to oncogenesis by achieving transforming functions, which induce hepatocarcinogenesis. Additionally, HBx can modulate apoptosis and immune response by direct or indirect interaction with host factors. We conclude that HBx hastens the development of hepatoma.