长非编码RNA BC032469调控胃癌细胞hTERT表达的分子机制研究

项目名称： 长非编码RNA BC032469调控胃癌细胞hTERT表达的分子机制研究

项目编号： No.81201950

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 吕沐瀚

作者单位： 中国人民解放军第三军医大学

项目金额： 24万元

中文摘要： 文献及我们的研究证实端粒酶逆转录酶(hTERT)的活化参与了肿瘤发生发展的全过程。目前有关hTERT转录后调控多集中在miRNA，而相关miRNA又是如何被调控的并不清楚。在国家自然科学基金资助下，我们发现多个miRNAs可以通过与hTERT 3'UTR结合抑制hTERT的表达，同时生物信息学分析发现hTERT基因附近的长非编码RNA BC032469 (lncRNA BC032469)与miRNAs的种子区有数个串联的互补序列，并发现上述miRNAs和lncRNA在胃癌组织中的表达呈负相关，提示lncRNA BC032469可能通过内源性"海绵效应"下调miRNAs，从而促进hTERT的表达.本课题拟采用荧光素酶实验、RNA干扰技术及动物实验等，阐明lncRNA调控miRNAs的分子机制及在hTERT活化中的作用，为基于hTERT的肿瘤防治提供新的靶点。

中文关键词： 长链非编码RNA；微小RNA；人端粒酶逆转录酶；胃癌；

英文摘要： In our previous study, it has been proved that the activation of hTERT participated in the whole process of tumor's genesis and development. Till now, relative research about post-transcriptional control of hTERT mostly concentrated on miRNA, while how miRNA is regulated remains to be unclear. Under the financial assistance of National Natural Sciences Fund, we found that multiple miRNAs can suppress the expression of hTERT by combining with hTERT 3'UTR. Meanwhile, by bioinformatics technology, it has been found that long non-coding RNA BC032469 (lncRNA BC032469) near hTERT gene together with seed area of miRNAs had several tandem complementary sequences; these miRNAs was negatively correlated to the expression of lncRNA in stomach cancer tissue, which indicated that lncRNA BC032469 may down-regulate miRNAs by endogenous sponge effect, then promoting the expression of hTERT. This study is planning to clarify the molecule mechanism of lncRNA controlling miRNAs and its role in the activation of hTERT, by luciferase experiment, RNA-interfering technique and animal experiment, etc. which will provide a new target point for tumor prevention and cure based on hTERT.

英文关键词： lncRNA；miRNA；hTERT；gastric cancer；