miR-592、NF-κB以及lncRNA在神经干细胞分化过程中的调控作用

项目名称： miR-592、NF-κB以及lncRNA在神经干细胞分化过程中的调控作用

项目编号： No.31271120

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 张军

作者单位： 同济大学

项目金额： 78万元

中文摘要： 核转录因子NFκB、某些非编码RNA，如miRNA、长链非编码RNA(lncRNA)都与神经干细胞的分化密切相关，但在神经干细胞分化过程中的作用尚不清楚。我们前期研究发现一条新的与神经干细胞定向分化有关的miR-592，可以通过抑制其靶基因Nkiras2表达，从而激活NF-κB的功能。生物信息学预测NFκB具有miR592基因启动子的结合位点，提示NFκB又可以促进miR592基因表达，形成一种正反馈调节。理论上预测，NFκB可促进某些lncRNA基因转录，而某些lncRNA与miR-592之间可能相互结合，又抑制了NFκB活性，形成了一种负反馈调节。本项目拟通过生物信息学、染色质免疫共沉淀(CHIP)、cDNA的5'RACE、EMSA等技术，研究miR-592，NFκB通路以及lncRNA之间的相互关系，绘制出三者之间的正向和负向调控网络，以阐明该网络对神经干细胞分化的调控机制。

中文关键词： 神经干细胞；神经元；分化；Nfasc；LncRNA

英文摘要： As the important transcriptional regulation molecular, some miRNAs, NF-κB and lncRNA are involved in the NSC differentiation. However, the interaction networks among them and the regulatory mechanism contributing to NSC differentiation are still not completely understood. In our previous study, we identified a new neural-enriched miRNA - miR-592, which may play an important role in neural stem cells specific differentiation. And miR-592 can affect the NFkB signal pathway through regulating its target gene - Nkiras2. It is predicted by bioinformatics that NF-κB contain a binding site of miR592 gene promotor. It suggested NF-κB could enhance the transcription. Meanwhile, it has been showed that NF-κB can regulate the expression of lncRNA by its regulatory mechanism at transcriptional level. And lncRNA can also control the miRNA expression by functioning as a competing endogenous RNA. In this study, we will use bioinformatics, ChIP, 5'RACE, EMSA approaches to investigate the interaction among miR-592, NF-κB and lnRNA, and to reveal the positive and negative regulatory loop among them, and its mechanism in NSC differentiation.

英文关键词： Neural stem cells；Neurons；differentiation；miRNA；LncRNAs