title: Hepatitis B surface antigen inhibits MICA and MICB expression via induction of cellular miRNAs in hepatocellular carcinoma cells.
abstract: Hepatitis B surface antigen (HBsAg) seropositivity is an important risk factor for hepatocellular carcinoma (HCC), and HBsAg-transgenic mice have been reported to spontaneously develop HCC. The major histocompatibility complex class I-related molecules A and B (MICA and MICB) are NKG2D ligands that play important roles in tumor immune surveillance. In the present study, we found that HBsAg overexpression in HepG2 cells led to upregulation of 133 and downregulation of 9 microRNAs (miRNAs). Interestingly, several HBsAg-induced miRNAs repressed the expression of MICA and MICB via targeting their 3'-untranslated regions. In addition, the expression of MICA and MICB was significantly reduced upon HBsAg overexpression, which was partially restored by inhibiting the activities of HBsAg-induced miRNAs. Moreover, HBsAg-overexpressing HCC cells exhibited reduced sensitivity to natural killer cell-mediated cytolysis. Taken together, our data suggest that HBsAg supresses the expression of MICA and MICB via induction of cellular miRNAs, thereby preventing NKG2D-mediated elimination of HCC cells.
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical College, 268 Xueyuan Road, Wenzhou, Zhejiang Province 325000, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wu
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Ren
authors.forename: Yi-Jiang
authors.initials: YJ
authors.lastname: Song
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Xue
authors.forename: Yu-Xiao
authors.initials: YX
authors.lastname: Fang
authors.forename: Zhu-Jun
authors.initials: ZJ
authors.lastname: Deng
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xu
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
authors.forename: Kai-Fu
authors.initials: KF
authors.lastname: Tang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000472:pathogenicity / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; D035683:MicroRNAs