Genome Scale Analysis of miRNA and mRNA regulation during preterm labor [whole blood]

The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age本研究旨在明确罹患特发性早产（idiopathic preterm labor, PTL）的女性外周血微小RNA（miRNAs）与信使RNA（mRNAs）之间的关联，并将其网络层面的表达变化与足月分娩的对照女性进行比较。作为安大略出生队列（Ontario Birth Study）的一部分，我们通过RNA测序（RNA Sequencing）对15名特发性早产女性与30名孕周匹配的非病理性对照女性的单核细胞及全血白细胞开展了全基因组miRNA和mRNA表达谱分析。我们已鉴定出与特发性早产相关的差异表达miRNAs、mRNAs及信号通路。值得注意的是，我们发现多个细胞信号通路存在扰动，尤以白细胞介素信号通路最为显著。此外，我们预测了特定miRNAs的靶mRNA，并基于这些预测结果构建了推测性的miRNA-mRNA调控网络。我们鉴定出6个与特发性早产显著相关的miRNAs，其表达水平与14个同样与特发性早产显著相关的预测靶mRNA的表达呈负相关。总体实验设计：对发生自发性早产临产的女性的全血及单核细胞中的miRNA和mRNA进行定量，并与孕周匹配的未临产对照女性进行对比。