Obstetrics and Gynecology Hospital, Fudan University, Shanghai, P.R. China.
Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, P.R. China.
Int J Mol Med. 2014 May;33(5):1250-60. doi: 10.3892/ijmm.2014.1691. Epub 2014 Mar 7.
microRNAs (miRNAs) are important both in early cardiogenesis and in the process of heart maturation. The aim of this study was to determine the stage-specific expression of miRNAs in human fetal heart in order to identify valuable targets for further study of heart defects. Affymetrix microarrays were used to obtain miRNA expression profiles from human fetal heart tissue at 5, 7, 9 and 23 weeks of gestation. To identify differentially expressed miRNAs at each time-point, linear regression analysis by the R limma algorithm was employed. Hierarchical clustering analysis was conducted with Cluster 3.0 software. Gene Ontology analysis was carried out for miRNAs from different clusters. Commonalities in miRNA families and genomic localization were identified, and the differential expression of selected miRNAs from different clusters was verified by quantitative polymerase chain reaction (qPCR). A total of 703 miRNAs were expressed in human fetal heart. Of these, 288 differentially expressed miRNAs represented 5 clusters with different expression trends. Several clustered miRNAs also shared classification within miRNA families or proximal genomic localization. qPCR confirmed the expression patterns of selected miRNAs. miRNAs within the 5 clusters were predicted to target genes vital for heart development and to be involved in cellular signaling pathways that affect heart structure formation and heart-associated cellular events. In conclusion, to the best of our knowledge, this is the first miRNA expression profiling study of human fetal heart tissue. The stage-specific expression of specific miRNAs suggests potential roles at distinct time-points during fetal heart development.
微小 RNA（miRNAs）在早期心脏发生和心脏成熟过程中都很重要。本研究的目的是确定人胎心中 miRNA 的阶段特异性表达，以鉴定进一步研究心脏缺陷的有价值的靶标。使用 Affymetrix 微阵列从 5、7、9 和 23 孕周的人胎心中获得 miRNA 表达谱。为了在每个时间点识别差异表达的 miRNA，使用 R limma 算法进行线性回归分析。使用 Cluster 3.0 软件进行层次聚类分析。对来自不同簇的 miRNA 进行基因本体论分析。鉴定 miRNA 家族和基因组定位的共性，并通过定量聚合酶链反应（qPCR）验证来自不同簇的选定 miRNA 的差异表达。总共在人胎心中表达了 703 个 miRNAs。其中，288 个差异表达的 miRNAs 代表了具有不同表达趋势的 5 个簇。几个聚类的 miRNAs 在 miRNA 家族或近端基因组定位内也具有分类。qPCR 证实了所选 miRNAs 的表达模式。5 个簇内的 miRNAs 被预测为对心脏发育至关重要的靶基因，并参与影响心脏结构形成和心脏相关细胞事件的细胞信号通路。总之，据我们所知，这是第一个对人胎心中组织进行 miRNA 表达谱分析的研究。特定 miRNA 的特定阶段表达表明在胎儿心脏发育的不同时间点可能具有潜在作用。
