HBV suppresses expression of MICA/B on hepatoma cells through up-regulation of transcription factors GATA2 and GATA3 to escape from NK cell surveillance

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...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-08, Vol.7 (35), p.56107-56119
Main Authors: Guan, Yun, Li, Weiqun, Hou, Zhaohua, Han, Qiuju, Lan, Peixiang, Zhang, Jian, Tian, Zhigang, Zhang, Cai
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - immunology
Chromatin Immunoprecipitation
CpG Islands - genetics
Down-Regulation
Flow Cytometry
GATA2 Transcription Factor - metabolism
GATA3 Transcription Factor - metabolism
Hep G2 Cells
Hepatitis B virus - genetics
Hepatitis B virus - immunology
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class I - metabolism
Humans
Immunologic Surveillance
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Liver Neoplasms - immunology
Promoter Regions, Genetic - genetics
Protein Multimerization
Research Paper: Immunology
Trans-Activators - immunology
Trans-Activators - metabolism
Transfection
Tumor Escape - immunology
Up-Regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.11271