永久性房颤的转录组分析及miRNA调控网络的建立  

Permanent atrial fibrillation related transcriptome profiling and the establishment of miRNA regulatory network

作　　者：高杰[1] 周建[1] 顾松[1] 刘岩[1] 安向光[1] 张希涛[1] 苏丕雄[1] 

机构地区：[1]首都医科大学附属北京朝阳医院心外科,北京100020

出　　处：《基础医学与临床》2016年第9期1262-1267,共6页Basic and Clinical Medicine

摘　　要：目的探索永久性房颤(p AF)发病相关的关键miRNAs及其调控的靶基因。方法联合应用表达谱芯片和miRNA芯片分析p AF患者(n=7)和健康成人(n=4)的左房组织,筛选p AF相关差异表达的miRNAs,进行靶基因预测后,与表达谱芯片的筛选结果进行负相关分析后的基因集合进行显著性功能分析(GO-analysis);利用miRNA与靶基因之间的靶向调控关系,构建差异miRNA与交集靶基因的调控网络(miRNA-gene-network),得到网络中起核心调控作用的miRNA和被调控的关键靶基因;采用RT-q PCR方法检验另一组p AF患者(n=5)和健康成人(n=4)的左房组织标本。结果表达谱基因芯片发现610个mRNA有显著性改变(fold change>2,P<0.05),miRNA-靶基因调节网络发现与p AF显著相关的20个miRNAs和107个靶基因,相关度最高的是miR-144、miR-1284、miR-1827、miR-1、miR-3613-3p和miR-101;其调控的重要靶基因包括CACNB2、EFNB1、PTEN、TAOK1、RUNX1和TPM3等;RT-q PCR验证结果显示这些miRNAs和靶基因密切相关。结论通过表达谱基因芯片与miRNAs芯片联合分析p AF左房组织标本,构建miRNA调控网络,发现p AF重要的miRNA-靶基因调控及功能,结果更加准确。Objective To screen for the atrial fibrillation related miRNAs and their target gene and to find the path- ogenesis of permanent AF. Methods Left atrium miRNA and mRNA profiling in patients with permanent AF （ n = 7 ） were compared with healthy heart donors in sinus rhythm （n = 4 ） using microarrays. By predicting potential miRNA targets and making negative correlation analysis with differentially expressed mRNA, miRNA-target gene regulatory network was established, and key miRNA and target genes related with permanent AF were found, and RT-qPCR analysis was used to validate the expression of key miRNAs and gene in the network in another cohort. Bioinformatics analyses were performed to understanding the global regulating roles of miRNAs-gene network. Results 610 mRNAs （ fold change 〉 2, P 〈 0.05 ） were found to be significantly changed in permanent AF pa- tients compared with healthy controls. The target prediction and negative correlations analyses with the mRNA array have identified 20 dysregulated miRNAs and their 107 target genes. work were established. The miRNAs including miR-144, miR-1284, The corresponding miRNA-gene regulatory net- miR-1827, miR-1, miR-3613-3p and miR-101 and target genes containing CACNB2, EFNB1, PTEN, TAOK1, RUNX1 and TPM3 were found to be in the central part of the network. Some of their expressions were further verified by RT-qPCR analysis on another cohort. Conclu- sions Through the analysis of gene expression profile chip and miRNAs chip joint small sample of pAF left atrial tissue samples, a miRNA-gene network is described. The identification of pathogenesis of pAF based on important micrornas-target gene regulation and function may support a more accurate diagnosis.

关 键 词：永久性房颤 MICRORNA MRNA 靶基因 网络调控 

分 类 号：R541.75[医药卫生—心血管疾病]