Hepatitis B Virus X Protein Stimulates Proliferation, Wound Closure and Inhibits Apoptosis of HuH-7 Cells via CDC42
Hepatitis B Virus X Protein Stimulates Proliferation, Wound Closure and Inhibits Apoptosis of HuH-7 Cells via CDC42
复制标题
乙型肝炎病毒 X 蛋白通过 CDC42 刺激增殖、伤口闭合并抑制 HuH-7 细胞凋亡
DOI：
10.3390/ijms18030586
复制
发表时间：
2017-03-01
影响因子：
5.6
通讯作者：
Xu, Ping
中科院分区：
文献类型：
--
作者：
Xu, Yongru;Qi, Yingzi;Xu, Ping
慢性B型肝炎病毒（HBV）感染被认为是肝细胞癌（HCC）的主要病因。B型肝炎病毒X蛋白（HBx）已被报道是致癌的。HBV相关的HCC的潜在机制尚未完全了解，HBx蛋白在HBV诱导的癌发生中所起的作用仍然存在争议。CDC 42是Rho GT3家族的成员，据报道在几种不同的癌症中过表达，包括HBV相关的HCC。然而，CDC 42在HCC发展中的具体作用仍不清楚。在这里，我们研究了CDC 42负责由HBx介导的HuH-7细胞的更高增殖的细胞机制。我们发现，在HuH-7-HBx细胞中，CDC 42的表达水平及其活性显著增加。使用CRISPR/Cas9系统的CDC 42缺陷和特异性抑制剂卡辛的抑制导致HBx介导的增殖减少。此外，我们观察到含有GT3激活蛋白1（IQGAP 1）的IQ基序，其是CDC 42通路的下游介质，可能参与HBx诱导的致癌作用。因此，HBx/CDC 42/IQGAP 1信号通路可能在HBx介导的致癌作用中发挥重要作用。
Chronic hepatitis B virus (HBV) infection has been considered as the major cause of hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) has been reported to be oncogenic. The underlying mechanisms of HBV-related HCC are not fully understood, and the role played by the HBx protein in HBV induced carcinogenesis remains controversial. CDC42, a member of the Rho GTPase family, has been reported to be overexpressed in several different cancers, including HBV-related HCC. However, the specific role of CDC42 in HCC development remains unclear. Here, we investigated the cellular mechanisms by which CDC42 was responsible for the higher proliferation of HuH-7 cells mediated by HBx. We found that the expression level of CDC42 and its activity were significantly increased in HuH-7-HBx cells. The deficiency of CDC42 using the CRISPR/Cas9 system and inhibition by specific inhibitor CASIN led to the reduction of HBx-mediated proliferation. Furthermore, we observed that IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), the downstream mediator of the CDC42 pathway, might be involved in the carcinogenesis induced by HBx. Therefore, the HBx/CDC42/IQGAP1 signaling pathway may potentially play an important role in HBx-mediated carcinogenesis.