Abstract
BackgroundIt 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.MethodsThe 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.ResultsHBx 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.ConclusionsHBx promotes HCC cell metastasis by inducing EMT, which is at least partly mediated by lncRNAs.
Highlights
It has been widely accepted that hepatitis B virus X protein (HBx) plays an important role in hepatocellular carcinoma (HCC)
Of 47 HCC samples, the level of E-cadherin was lower in the HCC tissues with HBx (33 cases) than those without HBx (14 cases), whereas the level of vimentin was on the opposite side (Table 1)
The number and size of the metastatic tumours predominated in the HepG2-HBx group (Fig. 2f ).The immunocytochemical result indicated that the epithelial marker of E-cadherin was down-regulated, whereas the mesenchymal marker of vimentin was up-regulated in the HBx overexpressed HepG2 cells (Fig. 2g)
Summary
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. Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality worldwide [1]. Epithelial-mesenchymal transition (EMT) is an important mechanism for cancer metastasis and recurrence [8]. Lee et al found that HBx mediated the activation of STAT5b, which further improves cancer cell motility and invasiveness by inducing EMT in HCC [10]. Yang et al reported that HBx induced EMT by activating c-Src in HCC cells [11].
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