title: HBV suppresses expression of MICA/B on hepatoma cells through up-regulation of transcription factors GATA2 and GATA3 to escape from NK cell surveillance.
abstract: Decreased expression of NKG2D ligands on HBV-infected human hepatoma cells impairs NK cells lysis. However, which components of HBV exert this effect and the precise mechanisms need to be further investigated. In the present study, we observed that the HBx and HBc genes significantly down-regulated MICA expression. Through analysis with the chromatin immunoprecipitation assay, we found that HBV infection promotes the expression of transcription factors GATA-2 and GATA-3, which specifically suppressed MICA/B expression by directly binding to the promoter region of MICA/B. HBx protein, acting as a co-regulator, forms a tripolymer with GATA2 and GATA3, thus promotes the GATA-2 or GATA-3-mediated of MICA/B suppression. HBc protein inhibits MICA/B expression via directly binding to the CpG island in the MICA/B promoter. Thus, our study identified the novel role of transcription factors GATA-2 and GATA-3 in suppressing MICA/B expression and clarified the mechanisms of HBx and HBc in downregulation of MICA/B expression. These findings provide novel mechanisms for the contribution of HBV to hepatoma cells escape from NK cell surveillance.
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Han
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Peixiang
authors.initials: P
authors.lastname: Lan
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D015536:Down-Regulation; D005434:Flow Cytometry; D050989:GATA2 Transcription Factor / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D055503:Protein Multimerization; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D019139:Tumor Escape / Q000276:immunology; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: GATA-2; GATA-3; Immune response; Immunity; Immunology and Microbiology Section; MICA; hepatitis B virus; hepatocarcinoma