Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Background: interleukin-7 receptor (il-7r) is involved in the abnormal function of solid tumors,but the role and regulatory mechanisms of il-7r in hbv-related hepatocellular carcinoma (hcc) are still unclear. methods: gene and protein expression levels of il-7r were examined in hepatoma cells transfected with hepatitis b virus (hbv) plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein x (hbx). the expression of hbx and il-7r was measured by immunohistochemical analysis in hbv-related hcc tissues. the role of nf-κb and notch1 pathways in hbx-mediated expression of il-7r in hepatoma cells was examined. activation of il-7r downstream of intracellular signaling proteins akt,jnk,stat5,and the associated molecules cyclind1 and matrix metalloproteinase-9 (mmp)-9,was assessed in hbx-positive cells with or without treatment with il-7r short hairpin rna (shrna). additionally,the role of il-7r in hbx-mediated proliferation and migration of hepatoma cells was investigated. results: the expression of il-7r was increased in hepatoma cells transfected with hbv plasmids; hbx was responsible for the hbv-mediated upregulation of il-7r. compared to adjacent tissues,the expression of hbx and il-7r was increased in hbv-related hcc tissues. additionally,the relative expression levels of hbx were associated with il-7r in hbv-related hcc tissues. the activation of nf-κb pathways and expression of notch1 were increased in hepatoma cells transfected with hbx,and inhibition of nf-κb and notch1 pathways significantly decreased hbx-mediated expression of il-7r. the activation of akt and jnk and the expression of cyclind1 and mmp-9 were increased in hbx-positive cells. when cells were treated with il-7r shrna,the activation of akt and jnk,as well as the expression of cyclind1 and mmp-9,were significantly inhibited. additionally,il-7r was responsible for hbx-induced proliferation and migration ability of hepatoma cells. conclusions: our data demonstrate that hbx can upregulate il-7r via nf-κb and notch1 pathways to facilitate the activation of intracellular pathways and expression of associated molecules,and contribute to proliferation and migration of hepatoma cells. © 2016 the author(s).