长链非编码RNA-ASLNC02233在肝癌中的功能及机制研究

项目名称： 长链非编码RNA-ASLNC02233在肝癌中的功能及机制研究

项目编号： No.81201626

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 汪惠

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 肿瘤细胞中长链非编码RNA表达水平变化能影响下游基因表达从而引发肿瘤发生，目前肝癌中LncRNA的功能鲜有研究，作用机制也尚不清楚。本研究结合LncRNA/mRNA表达谱芯片和生物信息学分析整合筛选出肝癌中差异表达的LncRNA并构建共表达网络，从已知功能的mRNA推测LncRNA的作用。此外，我们验证了LncRNA-ASLNC02233在14对肝癌组织及8株肝癌细胞系中均有不同程度的表达下调，对ASLNC02233进行功能研究时发现干扰ASLNC02233，肝癌细胞的迁移、侵袭能力均显著增加。基于上述基础，我们将进一步研究ASLNC02233在肝癌中发挥功能的分子机制，寻找ASLNC02233的可能作用蛋白，探索其调控机制；本项目还将在大样本肝癌组织中检测ASLNC02233的表达水平，结合临床资料分析其与肝癌转移、预后、生存期等临床指标的相关性，为肝癌诊断提供参考。

中文关键词： 肝癌；长链非编码RNA；miR503HG；预后；转移

英文摘要： A handful of studies have implicated altered lncRNA levels can result in aberrant expression of downstream gene products that may contribute to tumorigenesis. However, the role of lncRNAs to hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain largely unknown, the molecular mechanisms of their functions are still lacking. In this study, we have identi?ed differentially expressed lncRNAs between HBV-related HCC and paired peritumoral tissues by lncRNA /mRNA microarray. We have built coding-noncoding gene co-expression network to identify interactions among lncRNAs in cancer tissues. Furthermore, we have find the corresponding mRNAs and developed the GO and pathway annotation in order to predict the function of lncRNAs. To validate microarray analysis ?ndings, we randomly selected lncRNAs among the differential lncRNAs and analyzed their expression using qRT-PCR in 14 pairs of HCC and corresponding nontumor liver tissues, as well as 8 HCC cell lines. The results confirmed that the LncRNA-ASLNC02233 was down-regulated in HCC tissues and cell lines with varying degrees. To investigate the roles of the ASLNC02233, we knockdown the ASLNC02233 expression by siRNA in Huh7 and SMMC-7721 cells, transwell assays indicated that the migration and invasion ability were significantly increased. This suggested

英文关键词： Hepatocellular carcinoma；lncRNA；miR503HG；Prognosis；Metastasis