2019 年第 5 期 第 14 卷

人体心肌内和血液中衰老相关长链非编码RNA的综合分析

Aging-related long chain non-coding RNA profile in human myocardium and blood

作者：田佳瑜程子超赵锦阳范谦

英文作者：

单位：100029首都医科大学附属北京安贞医院心内科北京市心肺血管疾病研究所

英文单位：

关键词：衰老；长链非编码RNA；mRNA；基因表达谱

英文关键词：

• 摘要：

• 【摘要】目的    探讨人类心肌和血液标本中长链非编码RNA（lncRNA）和mRNA的表达谱，分析人体心肌和血液标本中富集的与衰老相关的lncRNA，预测其潜在生物学功能和通路。方法    对19对祖孙（老年组和青年组）的38份血液样本和7例接受心脏手术患者的心肌组织进行lncRNA和mRNA基因微阵列分析，筛选老年组和青年组血液标本差异性表达的lncRNA和mRNA，对血液样本中的差异基因、血液样本中富集的基因及心肌组织样本中富集的基因求交集并绘制Venn图，对筛选出的心肌衰老相关的差异基因进行通路分析，利用共表达网络分析筛选出起核心作用的mRNA和lncRNA，并推测哪些mRNA和lncRNA之间具有调控关系。结果    在人类心肌标本中共检测到75 434个lncRNA和20 666个mRNA，在人类血液标本中共检测到75 434个lncRNA及20 666个mRNA，其中老年组与青年组差异性表达的lncRNA 2 835个，差异性表达的mRNA 959个。筛选血液标本中富集的lncRNA共24 281个、心肌标本中富集的lncRNA共23 980个与血液标本中具有衰老差异的lncRNA的交集，共得到可代表与心肌衰老相关的差异lncRNA 720个；筛选血液标本中富集的5 554个mRNA、心肌标本中富集的4 520个mRNA与血液标本中具有衰老相关差异的959个mRNA的交集，共得到可以代表与心肌衰老相关的差异mRNA 63个。通过共表达网络图辅助发现lncRNA与mRNA之间可能存在的作用关系，找到影响mRNA表达的lncRNA，有助于发现网络中起中心调控作用的lncRNA及其可能存在的新作用机制。结论    基因微阵列分析人类心肌和血液中lncRNA的表达谱，并对其进行潜在功能及通路的预测和分析，可为未来lncRNA和心肌衰老的相关研究提供参考及帮助。

• 【Abstract】Objective    To investigate the expression of long chain non-coding RNA(lncRNA) and microRNA(mRNA) in human myocardium and blood samples; to analyze the potential biological functions and pathways of aging-related lncRNA enriched in human myocardium and blood samples. Methods    Seven heart tissues from patients undergoing cardiac surgery and 38 blood samples from 19 pairs of grandfathers/grandsons were collected. LncRNA and mRNA were detected through microarray and the differential expression was analyzed between the elderly group(grandfathers) and young group(grandsons) to find targets. With Veen diagrams, the lncRNAs/mRNAs which were aging-related and enriched in blood and myocardium were found and the biological functions and pathways were predicted. Finally, the targets of aging-related lncRNAs/mRNAs in co-expression were postulated and described. Results    Totally 75 434 lncRNAs and 20 666 mRNAs were detected in myocardium; 75 434 lncRNAs and 20 666 mRNAs were detected in blood; 2 835 lncRNAs and 959 mRNAs showed significant differential expression between elderly group and young group. Taking the intersection among 24 281 lncRNAs enriched in blood samples, 23 980 lncRNAs enriched in myocardium and aging-related lncRNAs in blood; 720 myocardial aging-related lncRNAs were found. Among 5 554 mRNAs enriched in blood samples, 4 520 mRNAs enriched in myocardium and 959 aging-related mRNAs in blood; 63 myocardial aging-related lncRNAs were found. Co-expression of lncRNA and mRNA showed potential biological function and regulation between them; the lncRNA with central regulation role that affects mRNA expression and the possible mechanisms could be found. Conclusion    Microarray analyzing the expression profile of aging-related lncRNA provides valuable information of the potential biological functions and pathways in myocardial aging and senescence.