Interleukin-34 mediated by hepatitis B virus X protein via CCAAT/enhancer-binding protein α contributes to the proliferation and migration of hepatoma cells

Objectives Interleukin-34 (IL-34) is associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, the role and associated mechanisms of IL-34 in HBV-related HCC remain unclear. In this study, the expression, biological function and associated mechanisms of IL-34 in HBV-related HCC cells were investigated. Methods IL-34 expression induced by HBV and HBV X (HBX) gene was measured in hepatoma cells. The role of CCAAT/enhancer-binding protein alpha (CEBP/alpha) in HBX-induced IL-34 expression was examined. The signal pathways involved in the expression of CEBP/alpha and IL-34 induced by HBX were assessed. The role of IL-34 in the proliferation and migration of HCC cells, and related mechanisms were explored. Results Dependent on HBX, HBV increased IL-34 expression in hepatoma cells, and HBX upregulated and interacted with CEBP/alpha to enhance the activity of IL-34 promoters. CEBP/alpha mediated by HBX was associated with the activation of PI3-K and NF-kappa B pathways to promote IL-34 expression. Via CSF1-R and CD138, IL-34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl-xl and c-Myc mediated by HBX. Conclusion We demonstrate that IL-34 contributes to HBX-mediated functional abnormality of HCC cells and provides a novel insight into the molecular mechanism of carcinogenesis mediated by HBX.