microRNA expression profiling of the developing mouse heart
microRNA expression profiling of the developing mouse heart
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发育中的小鼠心脏的 microRNA 表达谱
DOI：
10.3892/ijmm.2012.1092
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发表时间：
2012-11-01
影响因子：
5.4
通讯作者：
Guo, Xi-Rong
中科院分区：
文献类型：
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作者：
Cao, Li;Kong, Li-Ping;Guo, Xi-Rong
MicroRNAs(MiRNAs)在调节正常器官的生理和发育中起着重要的作用。许多miRNAs在胚胎发生和器官发生过程中表现出空间和时间受限的表达模式。本研究旨在通过寡核苷酸连接和检测(Solid)miRNA筛选对小鼠胚胎心脏发育的4个关键时间点[胚胎日(E)12.5、E14.5、E16.5和E18.5]的miRNA图谱进行分析。4个时间点分别为M1组(E18.5)、M2组(E16.5)、M3组(E14.5)和M4组(E12.5)。选择在4个时间点之间具有一致折叠变化的miRNAs进行进一步分析。共鉴定出10个miRNAs(MMU-miR-23b、MMU-miR-24、MMU-miR-23a、MMU-miR-375、MMU-miR-29a、MMU-miR-93、MMU-miR-21、MMU-miR-25、MMU-let-7b和MMU-miR-27b)，占总读数的1%。没有miRNA持续下调或上调。用实时定量聚合酶链式反应检测到16个miRNAs在发育晚期组(M1+M2)和早期发育组(M3+M4)中有差异表达。与早期发育组相比，后期发育组let-7miRNA簇(MMU-let-7a/7d/7e/7f)的几个成员表达上调。对MMU-let-7a/7d/7e/7f预测靶点的网络分析确定了5个已知与心脏发育有关的靶基因(Foxp1、TBX5、HAND1、AKT2和PPARGCIA)。因此，本研究确定了几个在发育心脏中大量表达的miRNAs，其中几个在所研究的4个时间点有差异表达。这一分析结果可能因此阐明心脏正常发育的机制，并为未来先天性心脏病的研究提供生理学基础。
microRNAs (miRNAs) play an important role in regulating normal organ physiology and development. Many miRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the miRNA profile of the fetal mouse heart at 4 key time-points [embryonic day (E)12.5, E14.5, E16.5 and E18.5] in its development, by performing a sequencing by oligonucleotide ligation and detection (SOLiD) miRNA screen. The 4 time-points were designated as groups M1 (E18.5), M2 (E16.5), M3 (E14.5) and M4 (E12.5). miRNAs found to have consistent fold-changes of >2.0) between the 4 time-points were selected for further analysis. Ten miRNAs (mmu-miR-23b, mmu-miR-24, mmu-miR-23a, mmu-miR-375, mmu-miR-29a, mmu-miR-93, mmu-miR-21, mmu-miR-25, mmu-let-7b and mmu-miR-27b) that were the most highly expressed in the 4 groups, including the percentage >1% of total read counts, were identified. No miRNA was consistently downregulated or upregulated. There were 16 differentially expressed miRNAs between the later development group (M1+M2) and the early development group (M3+M4), which were valicated by quantitative real-time PCR. Several members of the let-7 miRNA cluster (mmu-let-7a/7d/7e/7f) were upregulated in the later development group compared with the early development group. A network analysis of the predicted targets of mmu-let-7a/7d/7e/7f identified 5 target genes (FOXP1, TBX5, HAND1, AKT2 and PPARGCIA), known to be involved in cardiac development. Therefore, this study identified several miRNAs that are abundantly expressed in the developing heart, several of which are differentially expressed in the 4 time-points studied. Findings of this analysis may thus clarify the mechanisms of normal heart development and provide a physiological basis for future studies on congenital heart disease.