长链非编码RNA SATB2-AS1调控SATB2表达介导结直肠癌转移的功能及分子机制研究

项目名称： 长链非编码RNA SATB2-AS1调控SATB2表达介导结直肠癌转移的功能及分子机制研究

项目编号： No.81472318

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： 王爽

作者单位： 南方医科大学

项目金额： 70万元

中文摘要： 长链非编码RNA（LncRNA）参与表观遗传调控等多种生物学过程，其异常表达及功能障碍在肿瘤发生发展中扮演重要角色。我们前期分析了结直肠癌演进过程中LncRNA的表达谱变化，从中筛选出一个与结直肠癌转移密切相关的LncRNA SATB2-AS1。经预实验验证，过表达SATB2-AS1能抑制结直肠癌细胞的增殖、运动和侵袭能力；且能调控结直肠癌转移相关基因SATB2的表达。但SATB2-AS1的确切功能及调控机制不清。本课题拟在前期工作基础上，利用基因转染、RNA干扰等体内、体外实验手段，进一步明确SATB2-AS1在结直肠癌转移中的功能；并应用RNA pull-down、RNA免疫沉淀、染色质免疫沉淀、报告基因检测等实验方法揭示SATB2-AS1对SATB2的调控机制及其介导结直肠癌转移的作用。本研究将为结直肠癌转移的预防和治疗提供新的策略，具有重要的科学意义和临床应用价值。

中文关键词： C08_结；直肠肿瘤；SATB2-AS1；长链非编码RNA；转移；SATB2

英文摘要： Long noncoding RNA (LncRNA) participates in many biological processes, such as epigenetic regulation, and their abnormalities have been confirmed to play critical regulatory roles in neoplasia. We analyzed different LncRNA expression profiles in progression of colorectal carcinoma (CRC) and selected out a novel LncRNA SATB2-AS1 associated with CRC metastasis in our previous studies. The preliminary function research has identified that the ectopic over-expression of SATB2-AS1 could inhibit the proliferation，invasiveness and mobility of CRC cells and that SATB2-AS1 could regulate the expression of SATB2 gene which associated with CRC metastasis. However,the contribution and functional mechanism of SATB2-AS1 to CRC remain unknown. In this study, we will evaluate the functions of SATB2-AS1 in CRC in vivo and in vitro through gain and loss of function model. Furthermore, we will explore the mechanism that SATB2-AS1 regulates SATB2 expression in CRC by RNA pull-down, Mass spectrometry, RNA immunoprecipitaiton (RIP), chromatin immunoprecipitation assay (ChIP), and luciferase reporter assay system. The research will provide new targets for therapy and preventing metastasis of CRC, which possessing the profound scientific implication and superb value for clinical application.

英文关键词： colorectal carcinoma;SATB2-AS1;long noncoding RNA;metastasis;SATB2