title: Hepatitis B virus whole-X and X protein play distinct roles in HBV-related hepatocellular carcinoma progression.
abstract: The role of HBV X protein (HBx) in the development of hepatocellular carcinoma (HCC) has been well studied. However, little is known about the molecular functions of HBV whole-X protein (HBwx), a protein fused with HBx and upstream 56 amino acid, in HCC. In current study, the molecular functions of HBwx in HCC pathogenesis has been investigated, as well as comparison between HBwx and HBx.
  
  
  
  Expression of HBwx and HBx in 50 HCC tissues was examined by immunohistochemistry. Their tumor-forming abilities were evaluated by an animal model and colony formation assay. Migration and invasion were detected by transwell assay and subcellular localization was tracked by GFP fluorescence. Cell proliferation, cell cycle and apoptosis were detected by CCK8 and FCM. Protein level was determined by Western blotting.
  
  
  
  HBwx was present in 72 % (36/50) of the liver tumor tissues and mainly expressed in the nucleus and deposited in the cytoplasm surrounding karyotheca. HBwx showed a promoting effect on tumorigenesis and growth in vivo and in vitro as well as cell migration and invasion, whilst such effect is compromised compared with that of HBx. Further analysis demonstrated differences in cell proliferation, cell cycle and cell apoptosis between cells expressing HBwx and those expressing HBx. Additionally, it was confirmed that RKIP-p-ERK pathway was involved in HBwx-related tumor formation.
  
  
  
  HBwx, with the extra 56 amino acids, is closely related with hepatocarcinogenesis, while displays different biological functions from HBx.
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.|Department of Gastroenterology, Xi'an Central Hospital, Xi'an, 710003, Shaanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Xi'an Eighth Hospital Affiliated to Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi Province, China. liuhonglili@hotmail.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
authors.forename: Ruitian
authors.initials: R
authors.lastname: Yi
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China. zhaoyingren@sohu.com.
authors.forename: Yingren
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China. sourmilk2003@163.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D006509:Hepatitis B / Q000150:complications* / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: HBV; HBV whole-X protein; HBx; HCC