Up-regulation of S100A4 expression by HBx protein promotes proliferation of hepatocellular carcinoma cells and its correlation with clinical survival

•Over-Expression of HBx accelerated the proliferation of HCC cell line.•S100A4 was upregulated in HBx over-expressed cells.•IFN-α2b can inhibit the expression of S100A4 and cell proliferation of HBx over-expressed cells.•Knockdown of S100A4 Expression repressed the cell proliferation.•HCC patients with higher S100A4 levels have lower survival rates. Hepatocellular carcinoma is one of the most common cancers worldwide. HBV-related HCC has characteristics of faster progression and worse prognosis. Previous studies have confirmed that HBx protein plays numbers of important roles in development of HBV-HCC. However, the molecular mechanism of carcinogenicity of HBx is still not well documented. Firstly, a HCC cell line over-expressing HBx was established and its function was verified. Subsequently, the differentially expressed genes were detected by transcriptome sequencing technology and use the Western Blot technology to detect the up-regulated genes in HBx overexpressed cells, and the functional correlation of the genes was analyzed. Finally, tissue microarray was used to correlate up-regulated gene with clinical follow-up data to verify correlation with clinical prognosis. Over-expression of HBx could promote cell proliferation, and over-expression of HBx could up-regulate the expression of S100A4 protein. ShRNA experiments showed that HBx promoted cell proliferation by upregulating the expression of S100A4. IFN-α2b can down-regulate the expression of S100A4 and inhibit the proliferation of HCC cells. The expression of S100A4 in cancer was significantly up-regulated compared with adjacent tissues, and was also significantly associated with tumors volume, the expression of PD-L1 and the survival time of patients with HCC. In general, S100A4 may be an effective therapeutic target for HBV-HCC. And the connection between S100A4 and HBV are not clear yet. This study may play a guiding role in the future clinical treatment of HCC.