环状RNA是一类新发现的、与多种疾病发生相关的非编码RNA，但其在急性髓细胞白血病（AML）中的致病机制尚不清楚。我们前期研究发现长链非编码RNA MEG3在AML发生中发挥重要作用（Leukemia,2017），在对AML样本进行转录组测序分析时发现环状RNA CDR1-AS在AML1/ETO（A-E）融合基因阳性的AML中高表达，过表达CDR1-AS可促进细胞增殖、抑制细胞凋亡；进一步研究发现CDR1-AS可通过与A-E蛋白结合并增强A-E蛋白稳定性促进A-E的表达。本项目将在前期研究基础上，利用RNA免疫共沉淀结合二代测序等技术，在细胞、动物模型及临床样本中，明确环状RNA CDR1-AS对具有A-E特征性融合基因的AML发生的影响，阐明环状RNA CDR1-AS通过与A-E蛋白结合促进A-E表达的分子机制，从而为寻找新分子靶标奠定理论基础，进一步为AML有效防治提供新策略。

Circular RNA is a newly discovered non-coding RNA that is associated with a variety of diseases, but its pathogenesis in acute myeloid leukemia (AML) is not yet known. In our previous study, we found that long non-coding RNA MEG3 plays an important role in the development of AML (Leukemia, 2017). Meanwhile, through the transcriptome sequencing analysis of AML samples revealed that the circular RNA CDR1-AS was highly expressed in AML harboring AML1/ETO fusion gene. Overexpression of CDR1-AS could promote the growth of AML cells and inhibit its apoptosis. Further studies had found that CDR1-AS could promote the expression of A-E by binding to A-E protein and enhancing the stability of A-E protein. Based on the previous studies, we will use RNA immunoprecipitation combined with second-generation sequencing techniques to study the effects of CDR1-AS on AML with AML1/ETO fusion genes in cells, animal models, and clinical samples. To elucidate the molecular mechanism by which circular RNA CDR1-AS promotes A-E expression by binding to A-E protein, so as to lay a theoretical foundation for finding new molecular targets and further provide new strategies for the effective prevention and treatment of AML.