lncRNA Rian在肺癌发生中的作用及与miR-370互作机制研究

项目名称： lncRNA Rian在肺癌发生中的作用及与miR-370互作机制研究

项目编号： No.31501046

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 覃丽梅

作者单位： 佛山科学技术学院

项目金额： 20万元

中文摘要： 非编码RNA的异常表达引起细胞内癌基因或抑癌基因受到异常调控从而导致肿瘤发生。我们前期的研究发现印记基因lncRNA Rian位于小鼠基因组最重要的基因调控区Dlk1-Gtl2内，并在多种癌症包括肺癌肿瘤中显著上调，Rian编码的miR-370是肺癌发生中的癌基因并可能与Rian相互作用。这些结果提示Rian在肺癌发生中具有作用但机理不明。为阐明Rian在肺癌发生中的作用及机制，本项目拟在Lewis肺癌模型上，通过超表达、shRNA干扰、基因缺失细胞株、miRNA封闭海绵、慢病毒感染等手段，在体外和体内两个水平研究Rian在肿瘤发生中的作用；同时研究Rian和miR-370相互调节和相互作用机制，并探讨该互作机制对肺肿瘤发生的影响。上述研究不仅为阐明Rian在肺癌中的作用提供实验依据，还为探讨lncRNA与自身编码的miRNA在肿瘤发生过程中的互作和调节机制提供新的认识。

中文关键词： 动物；非编码RNA；肿瘤发生；Rian；miR-370

英文摘要： Abnormal expression of non-coding RNA cause dysregulated expression of cellular oncogenes and tumor suppressors leading to tumorigenesis. Our previous study haves shown lncrna Rian locates in Dlk1-Gtl2 genomic region, which is the most important gene regulating loci, meanwhile, Rian significantly upregulated in various tumor including lung cancer; miR-370 coding by Rian act as tumor suppressor and can interact with Rian. These findings suggest Rian have effect in lung cancer but the mechanism is unclear. To investigate the role and mechanism of Rian, this project is ready to study the role of Rian during lung tumorigenesis by using overexpression, shRNA interference, gene knocking down cell line etc in both in vitro and in vivo level; meantime the crosstalk between miR-370 and Rian and the effect on tumorigenesis is also studied. These studies would offer the experiment data to clarifying the function of Rian, in addition, it can bring some novel understanding of crosstalk and feedback regulation mechanism between miR-370 and Rian.

英文关键词： Animal;Non coding RNA;Tumorigenesis;Rian;miR-370