title: Promoting effect of hepatitis B virus on the expressoin of phospholipase A2 group IIA.
abstract: BACKGROUND
  Hepatitis B virus (HBV) infection causes acute and chronic liver disease, ultimately leading to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Phospholipase A2 group IIA (PLA2G2A) plays important roles in the development and progression of many tumors. Thus far, there have been no reports on the association between HBV and PLA2G2A. The present study investigated the effect of HBV infection on PLA2G2A expression and its application in the diagnosis of HBV-related diseases.
  
  
  METHODS
  Serum levels of PLA2G2A in 308 HBV-infected patients and 185 healthy controls were measured using an enzyme-linked immunosorbent assay (ELISA). The difference in serum levels of PLA2G2A was analyzed among chronic hepatitis B (CHB), LC, and HCC patients. PLA2G2A mRNA and protein expression in HepG2 and HepG2.2.15 cells carrying the integrated HBV genome were measured using reverse transcription polymerase chain reaction (RT-PCR) and western blot assays. The HBV infectious clone pHBV1.3, the control plasmid pBlue-ks and PLA2G2A gene promoter were transfected into HepG2 and HepG2.2.15 cells. After transfection, the luciferase activity was measured in the cells. PLA2G2A mRNA and protein expression levels were examined using RT-PCR and western blot assays.
  
  
  RESULTS
  The serum levels of PLA2G2A were 258.3 ± 20.3ng/dl in the healthy controls and 329.0 ± 22.5ng/dl, 385.4 ± 29.3ng/dl and 459.2 ± 38.6ng/dl in the CHB, LC, and HCC patients, respectively. Statistical analyses revealed significantly higher serum levels of PLA2G2A in CHB, LC, and HCC patients than in the healthy controls (P < 0.05), and PLA2G2A levels were elevated in the order of HCC > LC > CHB group. High serum PLA2G2A levels in HCC patients were associated with a lower prevalence of lymph node metastasis and a lower TNM stage. HepG2.2.15 cells carrying the HBV genome expressed higher levels of PLA2G2A mRNA and protein than the HepG2 cells. In addition, HBV triggered PLA2G2A promoter activity and enhanced PLA2G2A mRNA and protein expression compared to the empty vector pBlue-ks.
  
  
  CONCLUSIONS
  HBV can upregulate the expression of PLA2G2A, and serum levels of PLA2G2A are associated with the progression of HBV-related diseases.
authors.affiliation: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
authors.forename: Chengliang
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratory, Shanghai Gongli Hospital, the Second Military Medical University, Pudong New Area, Shanghai, 200135, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
authors.forename: Bingzheng
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Shanghai Gongli Hospital, the Second Military Medical University, Pudong New Area, Shanghai, 200135, People's Republic of China. syliuxh@163.com.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D054501:Group II Phospholipases A2 / Q000097:blood / Q000235:genetics*; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000254:growth & development / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D008156:Luciferases; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human
keywords: Chronic hepatitis B; Hepatitis B virus; Hepatocellular carcinoma; Liver cirrhosis; Phospholipase A2 group IIA