100303491

ZEB2-AS1

Hepatocellular carcinoma (HCC) remains one of the most common types of cancer worldwide and prognosis remains poor. Previous studies have suggested that long noncoding RNAs (lncRNAs) may be key regulators of tumor development and progression in HCC. It has been determined that 6172% of transcribed regions contain lncRNAs in the antisense orientation (aslncRNAs). However, the function of aslncRNAs in HCC remains to be elucidated. The present study investigated the function of the aslncRNA zinc finger Ebox binding homeobox 2 antisense RNA 1 (ZEB2AS1) in 40 HCC tissues and 5 different human HCC cell lines using reverse transcriptionquantitative polymerase chain reaction. Additionally, the expression levels of ZEB2AS1 were downregulated by transfection of small interfering RNAs (siRNAs) to determine whether ZEB2AS1 is capable of affecting cell proliferation, invasion and metastasis by regulating ZEB2, vimentin, fibronectin, Ecadherin and Ncadherin expression levels. The results of the present study demonstrated that the expression levels of ZEB2AS1 were greater in HCC tissues when compared with the adjacent normal tissues. Furthermore, ZEB2AS1 expression was significantly associated with the size of the primary tumor, intrahepatic metastasis and tumor-node-metastasis stage. The KaplanMeier survival curves suggested that patients with high ZEB2AS1 expression levels experienced the lowest overall and recurrencefree survival rates compared with those that had low expression levels. In addition, the current study demonstrated that the downregulation of ZEB2AS1 was associated with decreased tumor growth and metastasis in HCC by the regulation of the expression levels of epithelial mesenchymal transition-induced markers. In conclusion, lncRNA ZEB2AS1 may be used as a valuable biomarker in patients with HCC.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: HBx promotes HCC cell metastasis by inducing EMT, which is at least partly mediated by lncRNAs.