MicroRNA可在转录后水平调节基因表达，于多种疾病中发挥重要作用。笔者发现 miR-18a-5p 在骨髓衰竭症（BMF）最经典疾病模型-再生障碍性贫血（AA）中表达低下，且预测到其靶基因为细胞分裂周期蛋白42（Cdc42）与共济失调-毛细血管扩张突变基因（ATM）。鉴于Cdc42可调节细胞形态、迁移、生长、增殖、凋亡及其转录激活等，及ATM对细胞自噬和端粒的调节作用，笔者推测miR-18a-5p可能借助调节Cdc42及ATM 参与AA的病理生理过程。本项目中，我们拟研究：①Cdc42介导的AA造血干细胞（HSC）和淋巴细胞各亚群增殖、周期、凋亡及趋化效应；②ATM对AA HSC自噬及端粒的影响；③miR-18a-5p与靶基因间的相互调节作用，以期阐明miR-18a-5p 介导的AA病理生理机制。并于动物模型体内验证上述体外研究结果，为以miR-18a-5p 为靶点的治疗策略提供理论依据

MicroRNAs are small-noncoding RNA molecules that post-transcriptionally regulate gene expression by degradation or translational repression. Recently, emerging evidence has demonstrated that miRNAs play important roles in a lot of diseases. Through detecting the expression profiles of microRNAs in aplastic anemia (AA) patients and normal controls, we found that miR-18a-5p was significantly lower in AA patients than that of controls. Further bioinformatics analyses showed that the target genes of this microRNA were cell division cycle protein 42 (Cdc42) and ataxia-telangiectasia-mutated (ATM). Cdc42 can regulate many important physiological processes, including cell morphology, migration, cell growth, proliferation, apoptosis, transcriptional activation and so on. Moreover, ATM is also involved in regulations of autophagy, telomere and DNA damage repairmen of hematopoietic stem cells. We hypothesize that miR-18a-5p is involved in AA by regulating Cdc42 and ATM. This project is herein aimed to elucidate the role of miR-18a-5p in pathology of AA, we will focus on the effects of Cdc42 and ATM on physiology of AA and the association between miR-18a-5p and target genes. Furthermore, we will validate the results of in vitro experiments by using AA mouse models, which will provide a theoretical basis of novel treatment strategy for AA.