长链非编码RNA-Zfas1在心肌梗死中的调控机制研究

项目名称： 长链非编码RNA-Zfas1在心肌梗死中的调控机制研究

项目编号： No.81470490

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张莹

作者单位： 哈尔滨医科大学

项目金额： 73万元

中文摘要： 心肌梗死是心源性猝死的主要原因，并且长链非编码RNA（lncRNA）在心血管疾病中发挥重要作用。本项目初步研究结果显示心肌梗死时心肌组织中一种lncRNA-Zfas1的表达水平显著增加，同时于心肌在体导入Zfas1重组慢病毒，小鼠心功能显著降低、心肌细胞出现钙超载。通过网络预测有6个转录因子和7个miRNA具有调控Zfas1基因的转录潜力，同时Zfas1具有调控涉及到离子通道、细胞凋亡等5个靶基因表达的潜力，因此Zfas1过表达是心肌梗死时电生理失衡和细胞损伤的重要原因。本项目将应用电生理学、分子生物学等手段阐明（1）心肌梗死时miRNA/转录因子-Zfas1-靶基因的调控网络；（2）首次以Zfas1为靶点应用基因沉默技术对心肌梗死进行预防和治疗，为心肌梗死的药物及基因治疗提供新思路和新措施；（3）确定外周血不同成分中Zfas1及ZF-miniRNA的表达特征，建立心肌梗死的早期预警体系。

中文关键词： 长链非编码RNA；心肌梗死；miRNA；转录因子

英文摘要： Myocardial infarction is a major cause of cardiac sudden death worldwide. The motality of it is still high due to no sensitive biomarker and effective treatment. So it need to explore the mechanism of myocardial infarction further and find new traget molecular. Recently, a new class of non-coding RNAs, long non-coding RNAs (lncRNAs) has been identified in a variety of eukaryotes. Although most remain functionally uncharacterized biological dark matter, lncRNAs have garnered considerable attention for their diverse roles in human biology. Now more researches have revealed that long non-coding RNA (lncRNA) play an important role in cardiovascular disease. Our previou study has shown that the expression of a lncRNA-Zfas1 is incresed significantly in myocardial tissue of myocardial infarction. Also transduction of cardiomyocytes by reconbination the lentiviral vector in co-expressing Zfas1 and green fluorescent protein (GFP) could impair the cardiac function and cause calcium overload. Further forecast by network has shown that 6 transcription factors and 7 microRNAs have potential to regulate the transcription of Zfas1 gene. Moreover, Zfas1 has a potential to regulate the expression of 5 target gene ranging from ion channel to apoptoisis. Therefore, over-expression of Zfas1 is an important reason for electrophysiological imbalance and cardiomyocyte damage. Based on these results, we will use a serious of molecular biological and electrophysiological techniques to carry out the following research: (1) the regulatory network of miRNA/transcription factor-Zfas1-target gene in myocardial infarction. (2) application of gene silencing technology based on Zfas1 to prevent and cure myocardial infarction. (3) to determine the expression charactor of Zfas1 and ZF-miniRNA in different components of peripheral blood, and to establish an early warning system of myocardial infarction.

英文关键词： lncRNA;myocardial infarction;miRNA;transcription factor