非小细胞肺癌相关LncRNAs的发现及其对靶向mRNAs的调控

项目名称： 非小细胞肺癌相关LncRNAs的发现及其对靶向mRNAs的调控

项目编号： No.81472175

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： 姜丽岩

作者单位： 上海交通大学

项目金额： 52万元

中文摘要： 肺癌是目前中国以及世界范围内最常见的恶性肿瘤，其中非小细胞肺癌更是在近几年增长迅速，因此研究其发病机制和发现早期诊断标志物具有重要意义。非编码RNA 参与了多种疾病尤其是肿瘤发生发展的调控过程，前期我们通过对非小细胞肺癌癌和癌旁组织全基因组表达谱数据的分析，发现一组在非小细胞肺癌中显著差异表达的LncRNAs。并且通过生物信息学预测，推断LncRNA-a可能是通过cis作用元件、LncRNA-b和LncRNA-c通过联合转录因子/染色质修饰复合物的机制靶向调控特定的mRNAs从而影响非小细胞肺癌的增殖凋亡、侵袭转移等恶性行为。本课题拟通过相关分子生物学实验探讨LncRNA-a,b,c如何通过上述作用方式，实现对mRNAs靶向调控，从而在非小细胞肺癌的发生发展过程中起到调控作用。最后，将在较大量的临床样本中鉴定LncRNA-a,b,c对非小细胞肺癌的诊断、治疗以及预后的临床意义。

中文关键词： C05_气管；支气管；肺肿瘤；长链非编码RNA；顺式反式调控；诊断标志物

英文摘要： Lung Cancer is the most frequent malignancy in China and all over the world. The major type of it, non-small cell lung cancer (NSCLC), is rapidly growing in recent years. Recent studies have shown that long noncoding RNAs (lncRNAs) play critical roles in multiple biological processes, including cancer development. In previous study we have identified a new set of lncRNAs by whole human transcriptome analysis in NSCLC tissues and their matched normal tissue counterparts. Results of bioinformatic analysis suggested that these lncRNAs might regulate their target genes expression through cis-activating and trans-regulating (interaction with transcription factors or chromatin modification complexes) mechanisms. Therefore we will verify the potential regulatory mechanisms and elucidate their effects on cell proliferation, apoptosis, migration and invasion phenotypes in NSCLC cells and in nude mice. Finally, we will examine the levels of lncRNA-a,b,c in a large group of normal and cancerous tissues of patients with NSCLC as well as in plasma samples of NSCLC patients and healthy controls. Overall, this project is intending to elucidate the regulatory mechanisms of lncRNA-a,b,c in NSCLC development and evaluate their potentialities in NSCLC diagnosis and prognosis.

英文关键词： Lung Neoplasms;LncRNAs;cis-/trans-activating;biomarker