Rett综合征（RTT）主要由MeCP2基因突变所引发。作为一个表观遗传调控蛋白，MeCP2调控的竞争性内源RNA（ceRNA）网络在Rett综合征中的功能未见相关报道。在前期实验中，我们使用RTT病人来源的iPSCs细胞分化成为RTT神经元，然后进行了全转录组RNA-seq测序以及lncRNA-miRNA-mRNA ceRNA网络分析。根据生物信息学分析的结果以及分子生物学的验证，我们提出lncRNA（SNHG3）可能作为ceRNA参与Rett综合征的病理发生。在本次申请中，我们一方面将在活体动物体内解析SNHG3/miR-340/Myt1通路对神经发育和功能的调节作用；另一方面将观察lncRNA-SNHG3腺病毒能否减轻Rett综合征模型小鼠的疾病表型。本项目将会为我们深入了解Rett综合征的分子机制提供全新的线索，为推动Rett综合征的治疗提供新的靶点和思路。

MeCP2 is an epigenetic regulatory factor whose mutation is associated with Rett syndrome (RTT). It is still unclear whether MeCP2 regulates the competitive endogenous RNA (ceRNA) transcriptional network in Rett syndrome. To explore the possible role of MeCP2 in RTT, we have performed a whole transcriptome analysis using RNA-sequencing and the lncRNA-miRNA-mRNA network analysis in neurons differentiated from the induced pluripotent stem cells (iPSCs) derived from RTT patients. According to the bioinformatics analysis and the validation of target genes, we discovered that the lncRNA-SNHG3 may act as the ceRNA which is involved in the pathogenesis of Rett syndrome. In this study, we will investigate the in vivo regulatory role of SNHG3/miR-340/Myt1 pathway in neurodevelopment and its biological functions. In addition, we will determine whether the adenovirus-mediated overexpression of lncRNA-SNHG3 can alleviate the phenotype of a mouse model of Rett syndrome. This study will not only provide deeper understanding of the molecular mechanism of Rett syndrome, but also identify new therapeutic targets for the treatment of this disease.