microRNA Profiling of Amniotic Fluid: Evidence of Synergy of microRNAs in Fetal Development.
microRNA Profiling of Amniotic Fluid: Evidence of Synergy of microRNAs in Fetal Development.
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羊水的 microRNA 分析：microRNA 在胎儿发育中协同作用的证据
DOI：
10.1371/journal.pone.0153950
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ling S
中科院分区：
文献类型：
--
作者：
Sun T;Li W;Li T;Ling S
羊水（AF）不断与胎儿交换分子，特别是通过其复杂的成分在胎儿发育中发挥关键作用。在这些组分中，微RNA被认为在装载在微泡中的细胞之间转移。然而，AF microRNA的功能仍然未知。迄今为止，很少有研究检测羊水中的microRNA。在这项研究中，我们采用miRCURY锁定核苷酸阵列来分析胚胎E13，E15和E17小鼠AF中microRNA的动态表达。在这些时间点，233个microRNA差异表达（p< 0.01），占小家鼠microRNA总量的23%。这些差异表达的microRNA根据其表达模式分为两组。基因本体分析表明，这些差异表达microRNA的交叉靶基因主要分布在突触、突触体、细胞突起和细胞骨架中。通路分析显示，两组microRNA的靶基因协同富集在轴突导向、粘着斑和MAPK信号通路中。MicroRNA-mRNA网络分析和基因定位表明，这些microRNA协同调节细胞运动、细胞增殖和分化，特别是轴突导向过程。与生长和增殖相关的癌症途径也在AF中富集。总之，本研究的结果首次显示了microRNA在胎儿发育过程中在AF中的功能，为解释AF microRNA在胎儿发育中的作用提供了新的见解。
Amniotic fluid (AF) continuously exchanges molecules with the fetus, playing critical roles in fetal development especially via its complex components. Among these components, microRNAs are thought to be transferred between cells loaded in microvesicles. However, the functions of AF microRNAs remain unknown. To date, few studies have examined microRNAs in amniotic fluid. In this study, we employed miRCURY Locked Nucleotide Acid arrays to profile the dynamic expression of microRNAs in AF from mice on embryonic days E13, E15, and E17. At these times, 233 microRNAs were differentially expressed (p< 0.01), accounting for 23% of the total Mus musculus microRNAs. These differentially-expressed microRNAs were divided into two distinct groups based on their expression patterns. Gene ontology analysis showed that the intersectional target genes of these differentially-expressed microRNAs were mainly distributed in synapse, synaptosome, cell projection, and cytoskeleton. Pathway analysis revealed that the target genes of the two groups of microRNAs were synergistically enriched in axon guidance, focal adhesion, and MAPK signaling pathways. MicroRNA-mRNA network analysis and gene- mapping showed that these microRNAs synergistically regulated cell motility, cell proliferation and differentiation, and especially the axon guidance process. Cancer pathways associated with growth and proliferation were also enriched in AF. Taken together, the results of this study are the first to show the functions of microRNAs in AF during fetal development, providing novel insights into interpreting the roles of AF microRNAs in fetal development.