标题:HBV suppresses expression of MICA/B on hepatoma cells through up-regulation of transcription factors GATA2 and GATA3 to escape from NK cell surveillance
作者:Guan, Yun; Li, Weiqun; Hou, Zhaohua; Han, Qiuju; Lan, Peixiang; Zhang, Jian; Tian, Zhigang; Zhang, Cai
作者机构:[Guan, Yun; Li, Weiqun; Hou, Zhaohua; Han, Qiuju; Lan, Peixiang; Zhang, Jian; Zhang, Cai] Shandong Univ, Inst Immunopharmacol & Immunotherapy, Sch Pha 更多
通讯作者:Zhang, C
通讯作者地址:[Zhang, C]Shandong Univ, Inst Immunopharmacol & Immunotherapy, Sch Pharmaceut Sci, Jinan, Shandong, Peoples R China.
来源:ONCOTARGET
出版年:2016
卷:7
期:35
页码:56107-56119
DOI:10.18632/oncotarget.11271
关键词:hepatitis B virus; MICA; hepatocarcinoma; GATA-2; GATA-3; Immunology and; Microbiology Section; Immune response; Immunity
摘要: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.
收录类别:SCOPUS;SCIE
WOS核心被引频次:1
Scopus被引频次:1
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984921009&doi=10.18632%2foncotarget.11271&partnerID=40&md5=360b25bd5127cf741b2b8a9bd9ef35f0
TOP