非编码RNA调控Lhx8的表达在基底前脑胆碱能神经系统损伤中的保护作用

基底前脑胆碱能神经系统参与了学习与记忆形成的过程，该系统的损伤可导致认知功能的障碍；假如能够对损伤后的分子机制进行系统研究，就可以针对性地对其进行功能修复。我们的前期研究发现，Lhx8作为一个核心转录因子在胆碱能神经元定向分化中起重要作用；而非编码RNA(miR17、miR20a和LncRNA H19)能够直接或间接地调控Lhx8的表达水平；在此基础上我们提出胆碱能神经系统的H19/microRNAs/Lhx8轴向调控假说，即：LncRNA H19能够作为竞争内源性RNA(ceRNA)调节miR17、miR20a与Lhx8 3’UTR的结合，从而在转录后水平影响Lhx8的蛋白翻译。本项目拟在验证该假说的基础上，将非编码RNA作为“内源性保护靶点”或将非编码RNA修饰的神经干细胞作为“外源性种子细胞”，对损伤后不同病理阶段的基底前脑胆碱能神经系统进行针对性地修复。

Basal forebrain cholinergic nerves system involvs the process of learning and memory, the injury of this system leads to cognitive deficit. If we can understand the post-injuried molecular mechanism systematically, the functional repair of this system will be provided successfully. In our previous researches, Lhx8, as a key transcriptional factor, promots the cholinergic neuronal differentiation; and non-coding RNAs (including miR17, miR20a, LncRNA H19) controls the expression of Lhx8; so we assume the hypothesis of H19/microRNAs/Lhx8 axis, namely LncRNA H19, as a competing endogenous RNA(ceRNA), controls the combination of miR17、miR20a with Lhx8 3’UTR, then manipulates the protein expression of Lhx8 in post-transcripted process. This project will prove this hypothesis firstly, then based on different pathologic processes, the non-coding RNAs will be worked as “intrinsic protective targets” or the neural stem cells which modulated by non-coding RNAs will be worked as “extrinsic seed cells”, then using them to repair the post-injuried basal forebrain cholinergic nerves system.