Hepatitis B surface antigen inhibits MICA and MICB expression via induction of cellular miRNAs in hepatocellular carcinoma cells
Hepatitis B surface antigen inhibits MICA and MICB expression via induction of cellular miRNAs in hepatocellular carcinoma cells
复制标题
乙型肝炎表面抗原通过诱导肝细胞癌细胞中的细胞 miRNA 来抑制 MICA 和 MICB 的表达。
DOI：
10.1093/carcin/bgt268
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发表时间：
2014-01-01
期刊：
影响因子：
4.7
通讯作者：
Tang, Kai-Fu
中科院分区：
文献类型：
--
作者：
Wu, Jianmin;Zhang, Xue-Jiao;Tang, Kai-Fu
乙型肝炎表面抗原（HBsAg）血清阳性是肝细胞癌（HCC）的重要危险因素，已有HBsAg转基因小鼠自发发生HCC的报道。主要的组织相容性复合体i类相关分子A和B （MICA和MICB）是NKG2D配体，在肿瘤免疫监视中起重要作用。在本研究中，我们发现HBsAg在HepG2细胞中过表达导致133个microRNAs （miRNAs）上调，9个microRNAs下调。有趣的是，一些hbsag诱导的mirna通过靶向MICA和MICB的3-非翻译区来抑制MICA和MICB的表达。此外，MICA和MICB的表达在HBsAg过表达时显著降低，并通过抑制HBsAg诱导的mirna活性部分恢复MICA和MICB的表达。此外，hbsag过表达的HCC细胞表现出对自然杀伤细胞介导的细胞溶解的敏感性降低。综上所述，我们的数据表明，HBsAg通过诱导细胞mirna抑制MICA和MICB的表达，从而阻止nkg2d介导的HCC细胞消除。
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.