MiR-221调控CXCL12/CXCR4生物轴诱导NKT细胞浸润致HBV相关HCC的发病机制

项目名称： MiR-221调控CXCL12/CXCR4生物轴诱导NKT细胞浸润致HBV相关HCC的发病机制

项目编号： No.81501818

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 唐翌姝

作者单位： 重庆医科大学

项目金额： 18万元

中文摘要： HBV感染与肝细胞肝癌（HCC）的发生有关，但致病机制尚不清楚。我们前期发现HBX蛋白可以上调miR-221导致HCC的发生，相关成果已发表SCI论文。HBX能上调CXCL12/CXCR4生物轴，生物信息学分析显示miRNA-221存在与趋化因子CXCL12转录调控序列相结合的结构基础。预实验表明转染miR-221的HepG2细胞中的CXCL12表达上调。CXCL12的特异性受体CXCR4表达在NKT细胞。在HBV感染的小鼠模型中，NKT细胞参与介导肝硬化过程。预实验发现HBV感染的肝癌组织中的NKT细胞比例明显高于未感染HBV的肝癌组织。本项目以罹患HBV相关HCC的小鼠为模型，拟采用免疫印迹法，荧光素酶活性分析、流式细胞术，免疫组织化学染色和CHIP等方法探讨miR-221通过调控CXCL12/CXCR4致NKT细胞浸润导致HBV相关HCC发生的分子机制，为HCC的防治开辟新的途径。

中文关键词： 肝细胞肝癌；；miR-221；；CXCL12；CXCR4；乙型肝炎病毒

英文摘要： The HBV infection is related to Hepatocellular Carcinoma (HCC ),but the pathogenic mechanism is not clear yet. We have found HBX protein could upregulate the miR-221 to induce HCC, which has been published. HBX protein could upregulate CXCL12/CXCR4 axis. Bioinformatics analysis demonstrated that the 3’-UTR of human CXCL12 contains a conserved binding site for miR-221 in different species. Our experiment showed that CXCL12 in HepG2 cells transected miR-221 was up-regulated.The receptor of CXCL12 was CXCR4 which expressed on the NKT cell.NKT cell could induce liver cirrhosis on the HBV transgenic mice model. Our experiment showed the NKT ratio in liver tissue of HBV-related HCC was higher than the HCC without HBV infection. The programme may employ HBV-related HCC mouse as research model, and use the method and technology such as luciferase assay, EMSA and CHIP and so on to elucidate the molecular mechanism that HBX protein regulate the miRNA-221/ CXCL12/CXCR4 to induce HBV-related HCC .The research can provide the new molecular target in clinical HCC therapy.

英文关键词： HCC;miR-221;CXCL12;CXCR4;HBV