Abstract
To explore a novel function of a mutant of the hepatitis B virus X protein (HBx Delta 127) in the promotion of hepatoma cell migration. The effect of HBx Delta 127 and wild type HBx on the migration ability of hepatoblastoma HepG2 cells were examined using wound healing assays in stable transfection systems. The full-length osteopontin(OPN) promoter sequence was cloned into the pGL3-Basic plasmid. The promoter activities of OPN in stably HBx Delta 127-transfected hepatoblastoma HepG2 (HepG2-X Delta 127) and hepatocellular carcinoma H7402 (H7402-X Delta 127) cells were determined using luciferase reporter gene assays. The mRNA expression levels of OPN were detected by RT-PCR. And the effect of MK886, a specific inhibitor of 5-lipoxygenase (5-LOX), on OPN promoter activity and mRNA expression in HepG2-X Delta 127 and H7402-X Delta 127 cells were examined using luciferase reporter gene assays and RT-PCR, respectively. Finally, the migration ability of HepG2-X Delta 127 was observed after treatment with siRNA targeting OPN mRNA and HBx mRNA using wound healing assays. HepG2-X Delta 127 cells exhibited a greater capacity for wound repair compared to HepG2-X cells. The promoter activity and mRNA expression levels of OPN were also increased in HepG2-X Delta 127 and H7402-X Delta 127 cells. Moreover, MK886 abolished the HBx Delta 127-mediated upregulation of OPN. Wound healing assays demonstrated that the migration ability of HepG2-X Delta 127 cells can be suppressed by treatment with siRNA targeting OPN mRNA and siRNA targeting HBx mRNA. HBx Delta 127 strongly promotes hepatoma cell migration via activation of OPN involving 5-LOX.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China
HBxΔ127 strongly promotes hepatoma cell migration To investigate the function of HBxΔ127 in hepatoma cell migration, we examined HepG2-X and HepG2-XΔ127 cell migration ability
The wound healing assays showed that HepG2-XΔ127 cells exhibited a greater ability to repair the wound than did HepG2-X cells at 36 h post wounding (P
Summary
Infection by the hepatitis B virus (HBV) is a major risk factor for development of HCC[1]. The HBV genome includes four partially overlapping open reading frames termed the preC/C, P, preS/S, and X genes. Hepatitis B virus X protein (HBx) is encoded by the X gene, which contributes to the development of HCC[2]. HBx is an important regulator that has been shown to have multiple biological functions, including transcriptional activation of a variety of viral and cellular promoters, interaction with other proteins, mediation of cell proliferation, and activation of apoptosis[3,4,5]. Several studies have reported that HBx promotes invasion www.nature.com/aps Zhang X et al acid synthase (FAS)[15]. The role of HBxΔ127 in the promotion of cell migration, remains unclear
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