title: Hepatitis B virus inhibits the expression of CD82 through hypermethylation of its promoter in hepatoma cells.
abstract: The tumor suppressor gene CD82, also known as KAI1, may act as a general suppressor of metastasis in numerous types of cancer. It is hypothesized that downregulation of CD82 gene expression may be an important factor in the induction of hepatocellular carcinoma (HCC), however the mechanism for this requires further study. In the present study, the relative mRNA and protein expression levels of the CD82 gene were determined in HCC and adjacent non‑tumor tissues. The association between the CD82 gene and the hepatitis B virus (HBV) was also investigated, by quantitative polymerase chain reaction, western blotting, luciferase reporter assays and mass spectrometry with matrix‑assisted laser desorption/ionization time‑of‑flight mass array. CD82 expression was shown to be suppressed in response to HCC promoter methylation. Relative CD82 mRNA and protein expression levels were downregulated in HCC tissues (P<0.05). HBx protein inhibited CD82 promoter activity and subsequently the mRNA and protein expression levels. Furthermore, it was demonstrated that HBV could inhibit the expression of CD82 at the transcriptional level, and repress the activity of the CD82 promoter through hypermethylation. In addition, the methyl enzyme inhibitor 5‑aza‑CdR could induce the CD82 promoter activity and the relative expression level of CD82 mRNA, as observed by an increase in luciferase activity driven by the CD82 promoter. The observations of the present study suggest that hypermethylation of the CD82 promoter may be an event leading to the development of HCC. Low expression of CD82 is likely to be involved in tumor progression. HBV may inhibit the expression of CD82 through hypermethylation of the promoter in hepatoma cells.
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Bing
authors.affiliation: Department of Head and Neck Surgery, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Internal Medicine Oncology, Huangshi Central Hospital, Huangshi, Hubei 435005, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051861:Kangai-1 Protein / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D015534:Trans-Activators / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C497688:CD82 protein, human; D051861:Kangai-1 Protein; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein