长链非编码RNA MOTALA在肺腺癌发生发展中的作用和机制研究

项目名称： 长链非编码RNA MOTALA在肺腺癌发生发展中的作用和机制研究

项目编号： No.81472190

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： 李亚斐

作者单位： 中国人民解放军第三军医大学

项目金额： 68万元

中文摘要： 长链非编码RNA（lncRNA）在肿瘤发生发展中的重要性日趋受到重视，目前在肺癌中的研究还极少。我们通过lncRNA表达谱芯片和生物信息学分析，筛选到对肺腺癌和正常肺组织基因表达差异起重要作用的关键lncRNA- MOTALA。MOTALA位于MUC5B基因外显子中，预实验发现MOTALA在肺腺癌组织中表达上调，且与肿瘤的病理分期显著关联。结合文献、生物信息学分析和预实验结果，我们推测MOTALA转录后生成的lncRNA，可与某种靶蛋白结合，调控MUC5B或其他癌症相关基因的转录表达，从而参与肺腺癌的发生和发展。为验证上述假说，本项目拟从临床研究、分子、细胞、动物不同水平进一步明确MOTALA表达与肺腺癌临床特征的关系，探讨MOTALA对肺腺癌细胞生物学行为的影响及其机制，分析与MOTALA结合的靶蛋白分子及其生物学意义,为深入认识lncRNA在肺癌发病过程中的作用及机制提供新的理论依据。

中文关键词： C05_气管；支气管；肺肿瘤；长链非编码RNA；MOTALA；粘蛋白5B

英文摘要： The important role of long non-coding RNA (lncRNA) in tumorigenesis and development has gained increasingly more attention in recent years, but the studies on lncRNA in lung cancer are very rare. By using lncRNA microarray and bioinformatics analysis, we screened a key lncRNA-MOTALA which was found important for gene different expression between lung adenocarcinoma and normal tissues. MOTALA is located on the exon of MUC5B gene. MOTALA expression is up regulated in lung adenocarcinoma tissues and significantly associated with pathological stages. Based on the previous evidence, bioinformatics analysis and our pilot results, we hypothesize that the lncRNA transcribed by MOTALA could combined with some kind of target proteins, then regulate MUC5B or other cancer-related genes expression, and thus participate in the development and progression of lung adenocarcinoma. To verify this hypothesis, this project is designed to study the role of MOTALA in lung cancer from different perspectives, i.e. clinical study, molecule, cell and animal studies. Our aims are to further clarify the relationship of MOTALA expression with clinical features of lung cancer; to explore the effect of MOTALA on biological behavior of lung adenocarcinoma cells and its potential mechanisms; to analyze target protein molecules combining with MOTALA and their biological significance. This project will provide a new theoretical basis for further understanding of the role and mechanism of lncRNA in lung cancer pathogenesis.

英文关键词： Trachea; bronchus and lung cancer;long non-coding RNA;MUC5B overlapping transcript associated with lung adenocarcinoma;MUC5B