lncRNA-SNHG5通过影响Twist/Mi2/NuRD蛋白复合物活性调控胃癌EMT进展的研究

项目名称： lncRNA-SNHG5通过影响Twist/Mi2/NuRD蛋白复合物活性调控胃癌EMT进展的研究

项目编号： No.81502032

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： 赵连梅

作者单位： 河北医科大学

项目金额： 17万元

中文摘要： 上皮-间质转化（EMT）使肿瘤细胞获得易发生侵袭转移的表型，参与胃癌的恶性进展及不良预后。我们前期研究发现lncRNA-SNHG5通过影响MTA2的亚细胞定位而抑制胃癌的侵袭和转移。MTA2为核小体重塑去乙酰化酶复合物Twist/Mi2/NuRD的重要成员，与此复合物中EMT重要相关转录因子Twist直接结合。预实验研究发现, 在胃癌细胞中过表达SNHG5后细胞出现上皮细胞形态转变，E-cadherin和ZO-1表达升高而N-cadherin 和Vimentin表达下降。提示我们，SNHG5可能在胃癌EMT进展中发挥重要作用。 SNHG5是否通过与MTA2的结合参与胃癌的EMT进程？Twist/Mi2/NuRD复合物在SNHG5调控胃癌EMT进程中有何作用？具体的分子生物学机制如何？本研究将通过Co-IP、ChIP、EMSA、免疫荧光染色及裸鼠胃癌移植瘤模型中基因干预等方法解答上述问题。

中文关键词： 胃肿瘤；长链非编码RNA-SNHG5；上皮-间质转化；转移相关基因2；Twist/Mi2/NuRD；复合物

英文摘要： Epithelial-mesenchymal transition (EMT) is the process of tumor cells obtaining ability of invasion and migration, which participates in development and progression in tumors including gastric carcinoma (GC) and closely correlates with the prognosis and survival of GC patients. Previously studies indicated that long noncoding RNA SNHG5 could inhibit the ability of invasion and metastasis of GC cells through influencing subcellular location of tumor metastasis-associated gene 2 (MTA2). MTA2 is the vital component of proteins complex Twist/Mi2/NuRD, in which Twist is the most important transcription factor that regulated EMT and interact with MTA2 directly. Our previous results showed that epithelial cells morphology was shown in GC cells after overexpression of SNHG5; in addition, E-cadherin and ZO-1 were upregulated while N-cadherin and Vimentin were downregulated significantly. All these clues indicate that lncRNA-SNHG5 might play a important role in tumor EMT progression of GC. What’s the relationship between SNHG5 and EMT? Whether SNHG5 regulates the progression of EMT? How Twist/Mi2/NuRD complex participates in SNHG5 function for EMT and what’s the exact mechanisms? We attempt at explain these question by means of Co-IP, ChIP, EMSA, immunofluorescence and gene interference in GC xenograft model, for the purpose of discovering and establishing molecular targets of prevention and therapy in gastric cancer.

英文关键词： gastric carcinoma;lncRNA-SNHG5;EMT;MTA2;Twist/Mi2/NuRD complex