结直肠癌中TOP2A与ZNF148的竞争性内源性RNA调控机制和功能研究

项目名称： 结直肠癌中TOP2A与ZNF148的竞争性内源性RNA调控机制和功能研究

项目编号： No.81201936

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： 高显华

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 竞争性内源性RNA（ceRNA）调控是一种全新的调控机制，即不同基因的mRNA可以通过竞争性结合相同的microRNA（miRNA）而相互调控。我们前期的研究表明TOP2A在结直肠癌中表达增高，但是却发挥抑癌作用，其发挥抑癌作用的机制还不清楚。ZNF148是一种公认的抑癌基因，而且抑癌机制比较明确。生物信息学预测显示：TOP2A和ZNF148可与13个相同的miRNA结合，其中7个（含miR-101）已有报道在结直肠癌中表达。所以，TOP2A可能通过ceRNA机制调控ZNF148的表达，进而发挥抑癌作用。我们已经证实miR-101在ceRNA调控中的作用，本项目拟扩大样本量进一步研究miR-101和其它6个miRNA在ceRNA调控中的作用，并比较分析它们的作用异同；然后研究反向调控是否存在；接着在体内外研究信号通路和功能的变化情况；进一步完善TOP2A与ZNF148的ceRNA调控机制。

中文关键词： 结直肠癌；微小RNA；TOP2A；ZNF148；竞争性内源性RNA

英文摘要： Competing endogenous RNA（ceRNA）regulation mechanism, in which different mRNA molecules can regulate each other by competitive binding to identical microRNA(miRNA) molecules, is a totally new regulation mechanism. Our previous studies have demonstrated that Topoisomerase II alpha (TOP2A) is overexpressed in colorectal cancer and exhibits tumor suppressing activity, but the underlying mechanism is still unknown. ZNF148 is a well-known tumor suppressor gene, and the mechanism of tumor suppressing is well studied. Bioinformatics analysis showes that both TOP2A mRNA and ZNF148 mRNA could bind to 13 identical miRNA molecules. Among them, 7 miRNAs (including miR-101) have been reported to be detected in colorectal cancer. So, it is probable that TOP2A exhibits tumor suppressing activity by regulating the expression of ZNF148 through the ceRNA regulation mechanism. Moreover, we had proved the role of miR-101 in the ceRNA regulation between TOP2A and ZNF148. This study aims to further elucidate the role of miR-101 and 6 other miRNA molecules in the ceRNA regulation mechanism in a larger sample, and then to clarify the similarities and differences of the 7 miRNAs in the ceRNA regulation; and to verify whether the regulation is reciprocal; and to clarify the alteration of signal transduction pathways and biological effects

英文关键词： colorectal cancer；microRNA；TOP2A；ZNF148；ceRNA