Department of Pathology, Harbin Medical University, Harbin, 150081, China.
Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Virol J. 2017 Dec 19;14(1):238. doi: 10.1186/s12985-017-0903-5.
It has been widely accepted that hepatitis B virus X protein (HBx) plays an important role in hepatocellular carcinoma (HCC). This study aimed to explore the function of long non-coding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) induced by HBx.
The association between HBx and EMT markers was detected using immunohistochemistry in HCC tissues. The effect of HBx on HCC EMT was assessed through morphological analysis, transwell assay, metastatic in vivo study and detection of EMT markers. LncRNA microarray was used to screen the differently expressed lncRNAs. Small interfering RNA and Western blot were used to analyse the function and mechanism of the locked lncRNA.
HBx was negatively correlated with the epithelial marker E-cadherin but positively correlated with the mesenchymal marker vimentin in HCC tissues. HBx induced the mesenchymal phenotype and improved the metastatic ability of HCC cells. Meanwhile, HBx down-regulated E-cadherin, whereas it up-regulated vimentin. In HCC cells, HBx altered the expression of 2002 lncRNAs by more than 2-fold. One of them was ZEB2-AS1. Inhibition of ZEB2-AS1 can compensate for the EMT phenotype and reverse the expression of EMT markers regulated by HBx. Additionally, HBx affected the Wnt signalling pathway.
HBx promotes HCC cell metastasis by inducing EMT, which is at least partly mediated by lncRNAs.
乙型肝炎病毒 X 蛋白（HBx）在肝细胞癌（HCC）中发挥重要作用，这一观点已被广泛接受。本研究旨在探讨长链非编码 RNA（lncRNA）在 HBx 诱导的上皮间质转化（EMT）中的作用。
采用免疫组化法检测 HCC 组织中 HBx 与 EMT 标志物的相关性。通过形态分析、Transwell 实验、体内转移实验和 EMT 标志物检测评估 HBx 对 HCC EMT 的影响。采用 lncRNA 微阵列筛选差异表达的 lncRNA。采用小干扰 RNA 和 Western blot 分析锁定 lncRNA 的功能和机制。
HBx 在 HCC 组织中与上皮标志物 E-钙黏蛋白呈负相关，与间充质标志物波形蛋白呈正相关。HBx 诱导间质表型并提高 HCC 细胞的转移能力。同时，HBx 下调 E-钙黏蛋白，而上调波形蛋白。在 HCC 细胞中，HBx 使 2002 个 lncRNA 的表达增加 2 倍以上。其中之一是 ZEB2-AS1。抑制 ZEB2-AS1 可补偿 EMT 表型，并逆转 HBx 调节的 EMT 标志物的表达。此外，HBx 影响 Wnt 信号通路。
HBx 通过诱导 EMT 促进 HCC 细胞转移，至少部分通过 lncRNA 介导。
