ABSTRACT
Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). Kinesin family member 4A (KIF4A) is a microtubulebased motor protein, which is upregulated in cervical and lung cancer. However, the expression of KIF4A in HBVassociated HCC, and the effect of HBV on the expression of KIF4A remain to be elucidated. In the present study, the expression profiles of KIF4A were examined in cancerous tissues and paracancerous tissues from patients with HCC, who presented with histories of chronic HBV infection, and the role of HBV in the induction of the expression of KIF4A was investigated. HepG2 cells were transfected with the pHBV1.3, HBV infectious clone and a construct, which contained the luciferase gene under the control of the KIF4A gene promoter. The results demonstrated that the expression of KIF4A was significantly higher in the HCC tissues than in the paracancerous tissues. HBV activated the KIF4A gene promoter and upregulated the mRNA and protein expression of KIF4A. Furthermore, activation of the gene expression of KIF4A increased in a pHBV1.3 concentrationdependent manner. These results provide novel insights into the understanding of HCC oncogenesis caused by HBV.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Hepatitis B virus/physiology , Hepatitis B, Chronic/metabolism , Kinesins/genetics , Liver Neoplasms/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Gene Expression , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/genetics , Humans , Kinesins/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/virology , Male , Middle Aged , Promoter Regions, Genetic , Up-RegulationABSTRACT
BACKGROUND: Chronic liver diseases can interfere with hepatic metabolism of lipoproteins, apolipoproteins. Hepatitis B virus (HBV) is a major etiological agent causing acute and chronic liver diseases. Apolipoprotein M (ApoM) is a high-density lipoprotein (HDL) apolipoprotein and exclusively expressed in the liver parenchyma cells and in the tubular cells of the kidney. This study was to determine the correlation between HBV infection and ApoM expression. MATERIALS AND METHODS: Serum ApoM levels in patients with HBV infection and in healthy individuals were measured by ELISA, ApoM mRNA expression were determined by RT-PCR, and the expression of S and E proteins of HBV, as well as the synthesis of viral DNA were measured by ELISA and real-time PCR. RESULTS: The levels of serum ApoM was significantly elevated in patients as compared to healthy individuals (P < 0.001), ApoM promoter activity, mRNA and protein expression were all stimulated in cells transfected with infectious HBV clone. In addition, ApoM decreases the expression of S and E proteins of HBV and the synthesis of viral DNA. CONCLUSION: Raised ApoM levels in HBV infection may in turn suppress HBV replication, one of the protective mechanisms of nature.