hsa-circ-0000072在儿童AML中的表达、功能及调控机制研究

Recent studies have revealed circular RNAs（circRNA）play an important role in human disease through binding with miRNA. The research of circular RNA in leukemia has not yet been reported. By Arraystar circular RNA Microarray technology, we found that an circular RNA, hsa-circ-0000072 is elevated more than 100 times in pediatric acute myeloid leukemia(AML). It is predicted that the hsa-circ-0000072 contains miRNAs(miR-145 and miR-153) response element. We therefore hypothesize that hsa-circ-0000072 is highly expressed in pediatric AML, and acts as a miRNA(miR-145 and miR-153) sponge, of which miRNA are considered as “tumor suppressor gene”, and then result in activating c-Myc and Bcl-2 signaling pathways and drive tumorigenesis. In the proposed study, we will determine the hsa-circ-0000072 expression in pediatric AML, and study the biological roles of hsa-circ-0000072 on cell proliferation, differentiation and apoptosis in vitro.The completion of the proposed study will be expected to reveal the function of hsa-circ-0000072 and its role in pediatric AML. It could provide novel molecular targets as biomarkers for diognosis and targets for pediatric AML therapy.

最新研究表明环状RNA通过与miRNA结合，在疾病发生发展中起重要作用。目前环状RNA在白血病中研究尚未见报道。本课题组采用环状RNA芯片技术发现hsa-circ-0000072在儿童AML中增高100多倍，软件预测它具有miR-145和miR-153结合位点。提出假说：hsa-circ-0000072在儿童AML中高表达，通过吸附起“抑癌”作用的miR-145和miR-153，激活下游重要癌基因c-Myc和Bcl-2，导致AML发生。本项目拟检测hsa-circ-0000072在儿童AML中表达，体内外研究其对细胞增殖、分化及凋亡影响。本项目的完成将阐明hsa-circ-0000072在儿童AML中的表达及功能，不仅对揭示“RNA调控网络”具有重要意义，而且可能为AML诊治提供新的标志物和靶点