HBV/AFB1双暴露介导AKR1B10上调表达在肝细胞癌门静脉侵袭转移中的作用研究

项目名称： HBV/AFB1双暴露介导AKR1B10上调表达在肝细胞癌门静脉侵袭转移中的作用研究

项目编号： No.81502533

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： 齐鲁楠

作者单位： 广西医科大学

项目金额： 18万元

中文摘要： HBV/AFB1具有协同致肝癌作用已被公认，但是否具有“协同促肝癌转移作用”国内外未见明确报道。而我们前期研究发现：HBV/AFB1双暴露肝癌中AKR1B10明显高表达，与HBV/AFB1协同致细胞染色体7q33.1畸变或致AKR1B10-C299S位点突变有关；并且AKR1B10高表达患者，其门脉癌栓发生率高,预后差。由此我们假设：HBV/AFB1可通过介导AKR1B10高表达促进肝癌细胞门脉侵袭转移。本研究首先通过临床大样本论证HBV/AFB1双暴露、AKR1B10高表达、门脉癌栓形成三者的相关性；并采用体外细胞功能实验、体内动物模型深入探讨AKR1B10高表达对肝癌细胞门脉侵袭转移潜能的影响；最后运用功能基因芯片筛查分析AKR1B10调控肝癌侵袭转移的相关信号通路，以初步揭示AKR1B10的促转移机制，为“HBV/AFB1协同促肝癌转移学说”提供依据，也为肝癌转移的靶向治疗提供新思路

中文关键词： 乙肝病毒；黄曲霉毒素B1；醛酮还原酶家族1B10；肝细胞癌；门静脉癌栓

英文摘要： It has been recognized that the synergistic effect of HBV and AFB1 in hepatocarcinogenesis，however, it is still unclear whether these two factors can act synergistically to promote metastasis of HCC.In our prior studies, we found that the expression level of AKR1B10 was significantly higher in HBV/AFB1 double exposure HCC. The HBV/AFB1- induced 7q33.1 chromosomal alterations and the HBV/AFB1-induced AKR1B10 mutations in codon 299 (C249S) may be the main factors that lead to high expression of AKR1B10 in HBV/AFB1 double exposure HCC .We also found that the expression of AKR1B10 was significantly associated with occurrence of portal vein tumor thrombus(PVTT)，which suggested the synergistic effect of HBV and AFB1 can promote cancer cell portal vein metastasis by upregulating cell AKR1B10 expression.In this study, we first confirm the relation among expression of AKR1B10 , HBV/AFB1 double exposure and PVTT.Then, experiments in vivo and in vitro will be perform to investigate effects of AKR1B10 on metastasis potentials of HCC.Finally, expression microarray analysis will be progressed to apply to find genes related to metastasis which were regulated by AKR1B10 in HCC cells, to reveal the molecular mechanisms underlying of AKR1B10-induced metastasis.The study will provide an important basis for synergistic of HBV/AFB1 promote HCC metastasis, which will provide fresh ideas for gene therapy of metastasis in HCC.

英文关键词： Hepatitis C virus;Aflatoxin B1;Aldo-keto reductase family 1;member B10;;Hepatocellular carcinoma;portal vein tumor thrombus