Identification of genes and miRNA associated with idiopathic recurrent pregnancy loss: an exploratory data mining study

Wael Bahia,Salima Ferchichi,Anouar Abidi,Ismael Soltani,Anis Haddad,Samia Menif,Wassim Y Almawi

doi:10.1186/s12920-020-00730-z

Abstract

BackgroundRecurrent 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.MethodsmiRNAs 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.ResultsA 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.ConclusionsThe present study provides novel insights into the molecular mechanisms underlying RPL.

Highlights

Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication, with an incompletely understood pathology
These databases include Online Mendelian Inheritance in Man (OMIM: catalog of human genes and genetic disorders that is freely available and updated daily) [13], GeneCards [14], Orphanet [15], Genetic Association Database (GAD, database of genetic association data from complex diseases and disorders) [16], and HuGE Navigator [17]
P-match tool which is closely interconnected with the TRAN SFAC® database, was utilized in identifying DNA transcription factor binding sites (TFBS) [18]

Summary

Introduction

Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication, with an incompletely understood pathology. MicroRNAs (miRNA) are short (22–23 nucleotides) non-coding RNA, which regulate post-transcriptional activities [4], reportedly regulating ~ 60% of all proteincoding human genes, and are involved in diverse physiological processes and pathological states [5]. Their activity is attributed to their gene silencing capacity, by which miRNA binds > 100 target mRNA sites with partial base complementarity, preventing de novo translation, and/or accelerating mRNA degradation. Dysregulated miRNA expression was associated with physiological and pathological processes, including cellular differentiation, angiogenesis, apoptosis, and embryogenesis [9, 10]

Objectives

Methods

Results

Discussion

Conclusion