SIP1 serves a role in HBx-induced liver cancer growth and metastasis
SIP1 serves a role in HBx-induced liver cancer growth and metastasis
复制标题
SIP1 在 HBx 诱导的肝癌生长和转移中发挥作用
DOI：
10.3892/ijo.2019.4884
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发表时间：
2019-11-01
影响因子：
5.2
通讯作者：
Chen, Weixian
中科院分区：
文献类型：
--
作者：
Ye, Yuanyuan;Yang, Jun;Chen, Weixian
乙型肝炎病毒（HBV）已被发现参与肝细胞癌的发展。然而，其机制仍有待充分阐明。smad相互作用蛋白1 （SIP1）是一种转录抑制因子，在细胞转移中起关键作用。本研究探讨了SIP1在hbx诱导的肝细胞EMT和肿瘤侵袭性中的作用。我们发现HBV X蛋白（HBx）增加了SIP1的表达，并将其募集到E-cadherin的启动子上，从而抑制E-cadherin的转录。组蛋白去乙酰化酶1也被发现参与抑制复合物的形成。此外，在体内原位肿瘤移植模型中，HBx促进了肿瘤的生长和转移，而SIP1的下调则减弱了HBx的作用。这些结果提示了hbv相关肝癌发展的新机制。
Hepatitis B virus (HBV) has been revealed to be involved in the development of hepatocellular carcinoma. However, the mechanism remains to be fully elucidated. Smad-interacting protein 1 (SIP1) is a transcriptional repressor, which serves a pivotal role in cell metastasis. In the present study, the role of SIP1 in HBx-induced hepatocyte EMT and cancer aggressiveness was examined. It was found that HBV X protein (HBx) increased the expression of SIP1 and recruited it to the promoter of E-cadherin, resulting in depression of the transcription of E-cadherin. Histone deacetylase 1 was also found to be involved in the repressive complex formation. Furthermore, in an orthotopic tumor transplantation model in vivo, HBx promoted tumor growth and metastasis, whereas the knockdown of SIP1 attenuated the effect of HBx. These results indicate a novel mechanism for the development of HBV-related liver cancer.