LncRNA SNHG11在乙肝相关性肝癌发生发展中的作用

项目名称： LncRNA SNHG11在乙肝相关性肝癌发生发展中的作用

项目编号： No.81472282

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李楠

作者单位： 中国人民解放军第二军医大学

项目金额： 70万元

中文摘要： 肝癌是最常见的恶性肿瘤之一，乙肝病毒感染会显著增加罹患肝癌的风险。我们前期研究发现HBV可能通过调控LncRNA发挥作用，为探寻机制我们选取有乙肝和无乙肝的两组肝癌进行芯片筛选，结果提示LncRNA SNHG11和CLDN1在肝癌中呈特异性差异表达，且二者呈显著负相关。故设想LncRNA SNHG11是否通过调控CLDN1影响肝癌的进程？本课题拟构建LncRNA SNHG11 sponge转基因小鼠荷瘤模型；通过病毒/质粒转染上调和siRNA干扰下调LncRNA SNHG11，观察该变化是否反向调控CLDN1表达及下游信号通路，从而影响肝癌的恶性表型和进展；同时通过200例临床样本检测LncRNA SNHG11转录及CLDN1的表达情况，结合肝癌患者总体生存期及肿瘤复发情况，探寻LncRNA SNHG11与肝癌预后的关系，揭示乙肝相关性肝癌发生发展中关键LncRNA的作用。

中文关键词： 长链非编码RNA；肝细胞癌；乙型肝炎病毒

英文摘要： Hepatocellular carcinoma (HCC) is one of the most prevalent malignant neoplasms woldwide. Hepatitis B virus (HBV) is one of the major risk factors for occurrence of HCC. HBV infection increases the risk of HCC significantly. We found that HBV may play a role via regulating long non-coding RNA (lncRNA). Identifying differences between two groups of HCC with HBV and HCC without HBV, we found that lncRNA SNHG11(Homo sapiens small nucleolar RNA host gene 11) presented specific low expression in HBV-related HCC by the lncRNA microarray and CLDN1 presented specific high expression by gene microarray. Therefore, we assume that HBV effects CLDN1 expression in the tumor process by regulating lncRNA SNHG11. So we plan to establish a lncRNA SNHG11 sponge transgenic mice model with HCC. Through the virus/plasmid transfection and siRNA interference, we observe whether the regulation of lncRNA SNHG11 plays a role of the expression of CLDN1 and its downstream signaling pathways reversely and affects the malignant phenotypes and progress of HCC. And we detect lncRNA SNHG11 transcription and CLDN1 expression in the 200 pairs of clinical samples, combine with overall survival and tumor recurrence in these HCC patients, and reveal the role of the lncRNA SNHG11 in the occurrence and progress of HBV-related HCC.

英文关键词： Long non-coding RNA;Hepatocellular carcinoma;Hepatitis B Virus