摘要
目的:研究不稳定型心绞痛患者循环microRNA表达谱变化,及其通过神经生长信号通路的网络调控作用。方法:选取冠状动脉造影阴性的患者作为对照(n=6)和不稳定型心绞痛患者(n=6),抽取静脉血,提取全血microRNA,利用Taqman低密度微小RNA芯片检测microRNA表达,通过芯片数据分析工具SAM(significance analysis of microarray)得出显著差异表达microRNA。应用预测工具(Targetscan,miRanda,DIANA-micro T)得出不稳定型心绞痛相关microRNA的靶基因,应用芯片整合生物信息分析工具DAVID分析相关靶基因富集的信号通路,利用Panther数据库获取靶基因的生物功能聚类,通过Cytoscape构建microRNA的靶基因功能网络。结果:不稳定型心绞痛患者循环血中显著上调了20个microRNAs,并且其主要靶向调节神经生长因子通路,靶基因的功能集中在信号传导、细胞增殖分化、细胞周期、免疫炎症、神经生长和活动、细胞凋亡。结论:差异表达上调的microRNA主要抑制调节神经生长因子通路,即抑制细胞增殖、免疫炎症、神经生长等,从而稳定动脉粥样硬化易损斑块。
Objective：To study microRNA profile alteration in unstable angina （UA） patients and its functional network via nerve growth factor （NGF） signaling pathway.Methods：Whole blood microRNAs were isolated from individuals with angiographically negative report （n =6） and UA patients （n =6）,Taqman low-density microRNA array was performed to detect the microRNA profile,and SAM tool was conducted to calculate the differential expressed microRNA.Bioinformatic prediction tools （Targetsan,Miranda,Diana-microT） were used to obtain microRNA target genes.Targets＇ enriched pathways were analyzed by DAVID and biological function clusters were figured out by Panther database.The functional network of microRNAs by Cytoscape was costructed.Results：In the study,20 microRNAs were significantly upregulated in the UA group were observed.Their main target signaling pathways were NGF,their target genes＇ functional clusters were in signal transduction,cell proliferation and differentiation,cell cycles,immunity and inflammation,neurogenesis,neuronal activity and apoptosis.Conclusion：To upregulate microRNAs in UA patients is a major way to inhibit NGF signaling pathways,whose function is to suppress cell proliferation and differentiation,immunity and inflammation,neuronal growth,etc.,and to stabilize the vulnerable atherosclerotic plaque.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2014年第6期868-874,共7页
Journal of Peking University:Health Sciences
基金
国家自然科学基金(81270274
81270276/H0206)
北京市自然科学基金重点项目(D141100003014002)
北京市自然科学基金(7122198)资助~~
