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非瓣膜性心房颤动相关微RNA的表达; Differential expressions of miRNAs in patients with nonvalvular atrial fibrillation
王坚刚 ; 孟旭 ; 韩杰 ; 李岩 ; 罗天戈 ; 王珺 ; 辛萌 ; 席建忠
刊名中华医学杂志
2012
关键词心房颤动 微RNAs 电重构 Atrial fibrillation MicroRNAs Electric remodeling
DOI10.3760/cma.j.issn.0376-2491.2012.26.006
英文摘要目的 筛选、分析与非瓣膜性心房颤动(房颤)相关的微RNA(miRNA).方法 选择2009年1月至2010年12月北京安贞医院心外科的非瓣膜性房颤患者33例,应用低密度芯片技术,检测非瓣膜性房颤患者和健康人左心耳组织中miRNA表达谱的差异,用生物信息学方法筛选与房颤相关的miRNA及其靶基因,进一步通过定量反转录(RT)-PCR,Western印迹法和体外构建报告载体实验,验证miRNA和其靶基因之间的关系.结果 与健康人比较,房颤患者左心耳组织中发现10个差异表达的miRNA:miR-155、miR-142-3p、miR-19b、miR-223、miR-146b-5p、miR-486-5p、miR-301b、miR-193b和miR-519b表达高,miR-193a-5p表达低(均p<0.05);其中miR-155表达差异最大(9.42±4.74比1.63±0.65),为健康人组织的5.78倍.miR-155的高表达导致了预测的靶基因CACNA1C和相应Cav1.2蛋白的低表达,体外构建报告载体实验发现miR-155可以结合到CACNA1C的3’-UTR区.结论非瓣膜性房颤患者左心耳组织中存在与其发病相关的miRNA,其中miR-155有可能通过调控Cav1.2的表达,参与了房颤的电重构.; Objective To detect the differential expressions of miRNAs in left atrial appendage (LAA) in patients with atrial fibrillation (AF).Methods Left atrial samples were collected from nonvalvular AF patients and healthy controls.The miRNA transcriptome was analyzed by microarray and verified by real-time reverse transcription-polymerase chain reaction.Computational prediction identified the AF-related miRNAs and its target gene.In the meantime,construction of reporter plasmids and reporter assays were performed to test whether miRNA could represses the Luciferase activity of 3' untranslated regions of its target gene.Results MiR-155,miR-142-3p,miR-19b,miR-223,miR-146b-5p,miR-486-5p,miR-301b,miR-193b,miR-519b were found to be up-regulated by >2 folds whereas miR-193a-5p wasdown-regulated.In particular,the level of miR-155 increased by 5.78 folds in AF patients versus healthycontrols (9.42 ± 4.74 vs 1.63 ±0.65).Furthermore,computational prediction identified CACNAICencoding Cav1.2 as a direct target of miR-155.In the meantime,the construction of reporter plasmids andreporter assays showed that miR-155 repressed the Luciferase activity of 3' untranslated regions ofCACNAIC.Conclusion In LAA sample of nonvalvular AF,there is an expression of AF-related miRNAsincluding miR-155.And it reveals a potential link between the reglation of Cav1.2 and miR-155 in electricremodeling of AF.; 国家自然科学基金; 北京科技新星计划; 北京市卫生系统高层次卫生技术人才项目; 中文核心期刊要目总览(PKU); 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); 0; 26; 1816-1819; 92
语种中文
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/286021]  
专题工学院
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GB/T 7714
王坚刚,孟旭,韩杰,等. 非瓣膜性心房颤动相关微RNA的表达, Differential expressions of miRNAs in patients with nonvalvular atrial fibrillation[J]. 中华医学杂志,2012.
APA 王坚刚.,孟旭.,韩杰.,李岩.,罗天戈.,...&席建忠.(2012).非瓣膜性心房颤动相关微RNA的表达.中华医学杂志.
MLA 王坚刚,et al."非瓣膜性心房颤动相关微RNA的表达".中华医学杂志 (2012).
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