长链非编码RNA uc002bbp.2在 NSCLC顺铂耐药中的机制研究

项目名称： 长链非编码RNA uc002bbp.2在 NSCLC顺铂耐药中的机制研究

项目编号： No.81501961

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘晶

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 长链非编码RNA在非小细胞肺癌（NSCLC）顺铂耐药中起着重要的作用。课题组利用lncRNA高通量测序发现，lncRNA uc002bbp.2在NSCLC顺铂耐药细胞中的表达显著高于亲本细胞。封闭其表达后细胞对顺铂敏感性增加，PTEN的表达明显上调。前期研究表明PTEN与NSCLC耐药密切相关，而lncRNA可通过绑定PRC2复合物调控靶基因组蛋白H3K27位点甲基化沉默靶基因。课题组干扰PRC2核心亚基EZH2后，PTEN表达明显增加，细胞对顺铂敏感性增加。故此提出假设lncRNA uc002bbp.2可通过调控 PTEN启动子区甲基化沉默其表达，增加NSCLC顺铂耐药性。本项目拟在临床标本中检测lncRNA uc002bbp.2及PTEN与NSCLC耐药的相关性，并利用体内外实验进一步明确其调控PTEN在NSCLC中的作用及分子机制，为逆转临床NSCLC顺铂耐药提供新的理论依据及靶点。

中文关键词： 肺肿瘤；长链非编码RNA；uc002bbp.2；顺铂耐药

英文摘要： Long non-coding RNA plays a major role in non-small cell lung cancer (NSCLC) cisplatin resistance. Our previous study revealed that lncRNA uc002bbp.2 expression in NSCLC cisplatin-resistant cells was significantly higher than that of the parent cell by lncRNA high-throughput sequencing technology. Blocking lncRNA uc002bbp.2 could enhance sensitivity to cisplatin, and increase the expression of PTEN significantly. Our previous studies have demonstrated PTEN played an important role in NSCLC drug-resistant. Whereas lncRNA could bind PRC2 complexe to regulate histone H3K27 sites methylation of target gene, in turn coordinate to DNA methylation to silence the target gene. Interference the core subunit of PRC2 complexe (EZH2) could significantly increase PTEN expression and promote sensitivity to cisplatin. Therefore, we speculated that lncRNA uc002bbp.2 could silence PTEN expression by regulating promoter methylation to enhance cisplatin resistance of NSCLC. We intend to expand the clinical specimen validation to detect the correlation between lncRNA uc002bbp.2 and PTEN in NSCLC cisplatin resistance. We will explore the effects and molecular mechanisms involved in the regulation of PTEN expression by lncRNA uc002bbp.2 via in vivo and in vitro experiments, providing new basis and targets for reversing NSCLC cisplatin resistance.

英文关键词： lung cancer;lncRNA uc002bbp.2;cisplatin resistance