项目名称: 长链非编码RNA-MEG3调控EMT影响胃癌侵袭迁移分子机制研究
项目编号: No.81472714
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: 陈小兵
作者单位: 郑州大学
项目金额: 70万元
中文摘要: 胃癌是中国第二大常见恶性肿瘤,上皮间质转化(EMT)是胃癌侵袭转移研究的热点。研究表明,miRNA和长链非编码RNA(lncRNA)参与调控肿瘤EMT过程,但有关lncRNA调控胃癌EMT的研究甚少。在前一自然基金资助下,我们发现lncRNA-MEG3在胃癌组织中表达下调,进一步研究表明MEG3在TGF-β诱导后表达升高,并且过表达MEG3的胃癌细胞获得了EMT表型特征。这提示MEG3可能在胃癌EMT过程中发挥重要作用,但MEG3调控胃癌EMT的机制尚不清楚。本项目拟在前期工作基础上,以胃癌细胞株、胃癌细胞及病人癌组织来源裸鼠移植瘤模型、胃癌组织为研究对象,通过基因芯片、ChIP等技术,观察MEG3调控EMT对胃癌侵袭转移的影响,阐明MEG3调控胃癌EMT的分子网络机制,探讨MEG3与miRNAs的协调作用,为揭示胃癌侵袭转移机理、开发基于RNA的新型分子靶向药物提供理论依据。
中文关键词: C07_胃肿瘤;上皮间质转化;长链非编码RNA
英文摘要: Gastric cancer is the second most common malignant tumor in China. The major obstacle towards improved survival from gastric cancer is in the development of metastatic disease.Techniques in cellular and molecular biology have now advanced to the point to allow an examination of specific biomolecules in processes related to gastric cancer cell invasion. Latest research suggests the epithelial mesenchymal transitions(EMT)play an important role in gastric cancer metastatic development. miRNA as well as lncRNA were reported to regulate EMT processes, but there is not report about lncRNA and its role in gastric EMT processes.Our previous studies have found that long noncoding RNA MEG3 expressed in gastric cancer cut or missing, overexpression of MEG3 could inhibit the gastric cell growth and invasion, and display typical EMT phenotype characteristics.Further research shows that MEG3 expression was induced by TGF-β.Therefore, we presumed that MEG3 induced by TGF-βplay an important role in the metastases development of gastric carcinoma,and mechanisms is still unkwow. On the basis of our prior experiments, this study is intended to illustrate the role and molecular mechanism of MEG3 in process of tumorigenesis and development by as gene ChIP and ChIP, using cell line and tissue. Moreover, we intend to primarily indicate the MEG3 regulation mechanisms involved in the process of tumorigenesis and metastases development. The scientific meaning of this study lays emphases on enriching the understanding of tumorigenesis and development of gastric carcinoma, providing new target with high-effecacy for clinical treatment.
英文关键词: gastric cancer;epithelial mesenchymal transitions;ncRNA