Research Papers: Immunology:

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

Yun Guan _, Weiqun Li, Zhaohua Hou, Qiuju Han, Peixiang Lan, Jian Zhang, Zhigang Tian and Cai Zhang

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Oncotarget. 2016; 7:56107-56119. https://doi.org/10.18632/oncotarget.11271

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Yun Guan1, Weiqun Li1, Zhaohua Hou1, Qiuju Han1, Peixiang Lan1, Jian Zhang1, Zhigang Tian2 and Cai Zhang1

1 Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China

2 Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China

Correspondence to:

Cai Zhang, email:

Keywords: hepatitis B virus; MICA; hepatocarcinoma; GATA-2; GATA-3; Immunology and Microbiology Section; Immune response; Immunity

Received: March 30, 2016 Accepted: August 01, 2016 Published: August 12, 2016


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.

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