NET-1 promotes the proliferation of hepatocellular carcinoma cells via activating P13K/Akt and JAK2/STAT3 signaling pathways

Objective: This study aimed to investigate the association of neuroepithelial transforming gene-1 (NET-1) between its related signaling pathways in hepatocellular carcinoma (HCC) pathogenesis. Methods: HCC cells with relative higher NET-1 expression were transfected with NET-1 siRNA. Cell proliferation, apoptosis, and cell cycle were detected. Expression or activation of related signaling pathways was also detected. Results: NET-1 showed the highest expression level in SMMC 7721 cells and siRNA transfection downregulated NET-1 mRNA expression compared with control cells. Moreover, cells transfected with NET-1 siRNA decreased in cell proliferation by arresting cell cycle at G1 phase, decreased in expression of activated status factors of P13K/Akt and JAK2/STAT3 signaling pathways, Bcl-2 and cyclin D1. Whereas, NET-1 siRNA promoted SMMC 7721 cells apoptosis. Conclusions: Downexpression of NET-1 promoted cell apoptosis and inhibited cell proliferation via cyclin D1 mediated inactivation of JAK2/STAT3/ Bcl-2 and P13K/Akt/Bcl-2 signaling pathways in HCC cells. Inhibition of NET-1 might be explored as a potential therapeutic target for HCC.