胰腺癌中差异表达lncRNA的筛选及其功能研究

项目名称： 胰腺癌中差异表达lncRNA的筛选及其功能研究

项目编号： No.81472326

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： 陈杰

作者单位： 中国医学科学院北京协和医院

项目金额： 78万元

中文摘要： 长链非编码RNA（lncRNA）与人类疾病包括多种肿瘤有密切联系，最近有研究表明其可以受到microRNA（miRNA）的调控，但lncRNA在胰腺癌中的作用尚不清楚。本课题通过分析胰腺癌表达谱芯片数据，筛选出一批在胰腺癌中差异表达的lncRNA，并在胰腺癌细胞及组织中进行表达水平的验证；进而从功能缺失和功能获得两方面研究其对胰腺癌细胞生物学行为的影响，并用裸鼠体内实验进一步验证其功能。我们前期已发现了一批在胰腺癌发生过程中起到重要调控作用的miRNA分子，本课题在此基础上分析胰腺癌功能性lncRNA分子与这些miRNA分子的相互作用关系，并探讨两者与miRNA靶向蛋白之间的联系，构建lncRNA，miRNA，mRNA三者之间的基因调控网络，以进一步揭示胰腺癌的发生发展机制；同时检测胰腺癌患者及正常对照血清中三者的表达，筛选出胰腺癌特异性生物标志物，为胰腺癌的诊断治疗提供理论基础。

中文关键词： 胰腺癌；长链非编码RNA；微小RNA

英文摘要： Long noncoding RNAs (lncRNAs) have been discovered to play important regulatory roles in a variety of diseases, including many tumors. Recent studies demonstrated that lncRNAs could be regulated by microRNAs (miRNA). However, the functional roles of these transcripts in pancreatic cancer are not thoroughly understood. In this study, we plan to select a group of lncRNAs that are abnormal expressed in pancreatic cancer though data mining of publically available gene profiling results. Then we validated the expression level of selected lncRNAs in pancreatic cancer cell lines and paired pancreatic cancerous and normal tissues. To evaluate the possible role of selected lncRNAs in pancreatic cancer, we examine the effect of lncRNA downregulation or overexpression on the biological behavior of pancreatic cancer cell lines. Subsequently, an in vivo xenograft mouse model is included to validate the function role of selected lncRNA in pancreatic cancer. Our previous study showed that a number of miRNAs are involved in the carcinogenesis and progression of pancreatic cancer, so we explore the relationship between the functional lncRNAs and the miRNAs, and then further investigate the possible links among lncRNAs, miRNAs and also mRNAs. Finally, we detect the expression level of lncRNA, miRNA and mRNA in the serum of pancreatic cancer patients and normal controls in order to select early diagnosis or prognostic biomarkers for pancreatic cancer.

英文关键词： pancreatic cancer;long noncoding RNA;microRNA