Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication, with an incompletely understood pathology. While many entities were proposed to elucidate the pathogenic basis of RPL, only few were significant enough to warrant investigation in all affected couples.. The aim of this study was to provide novel insights into the biological characteristics and related pathways of differentially expressed miRNA (DEMs) and genes (DEGs), in RPL, and construct a molecular miRNAs–mRNAs network. miRNAs and gene expression data were collected, and a number of DEMs and (DEGs) were obtained, and regulatory co-expression network were constructed. Function and enrichment analyses of DEMs were conducted using DIANA-miRPath. DEGs were screened, and were used in generation of protein-protein interaction (PPI) network, using STRING online database. Modularity analysis, and pathway identification operations were used in identifying graph clusters and associated pathways. DEGs were also used for further gene ontology (GO) analysis, followed by analysis of KEGG pathway. A total of 34 DEMs were identified, and were found to be highly enriched in TGF-β signaling pathway, Fatty acid metabolism and TNF signaling pathway. Hub miRNAs were selected and were found to be involved in several functional pathways including progesterone-mediated oocyte maturation and Thyroid hormone signaling pathway. Five dysregulated feedback loops involving miRNA and TFs were identified and characterized. Most notably, PPI network analysis identified hub-bottleneck protein panel. These appear to offer potential candidate biomarker pattern for RPL diagnosis and treatment. The present study provides novel insights into the molecular mechanisms underlying RPL.

中文翻译：

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与特发性反复妊娠流产相关的基因和miRNA的鉴定：一项探索性数据挖掘研究。

反复妊娠丢失（RPL）是一种严重的不良妊娠并发症，其病理学尚未完全理解。尽管提出了许多实体来阐明RPL的致病基础，但只有极少数的实体具有足够的意义以致于需要对所有受影响的夫妇进行调查。 ）和基因（DEG），并构建一个分子miRNA-mRNA网络。收集miRNA和基因表达数据，获得许多DEM和（DEG），并构建调控共表达网络。使用DIANA-miRPath进行DEM的功能和富集分析。使用STRING在线数据库筛选DEG，并将其用于生成蛋白质-蛋白质相互作用（PPI）网络。模块化分析和路径识别操作用于识别图簇和相关路径。DEG还用于进一步的基因本体论（GO）分析，然后分析KEGG途径。总共鉴定出34个DEM，并且发现它们在TGF-β信号传导途径，脂肪酸代谢和TNF信号传导途径中高度富集。选择了Hub miRNA，发现它们参与了几种功能途径，包括孕激素介导的卵母细胞成熟和甲状腺激素信号传导途径。鉴定并鉴定了涉及miRNA和TF的五个失调的反馈环。最值得注意的是，PPI网络分析确定了枢纽瓶颈蛋白组。这些似乎为RPL诊断和治疗提供了潜在的候选生物标志物模式。