17-β estradiol signalling affects cardiovascular and cancer pathogenesis by regulating the crosstalk between transcription factors and EC-miRNAs

Abstract

Abstract 17β-estradiol (E2) or the bioactive form of estrogen has wide range of impact in regulating human physiology. It not only regulates organ development but also controls immune responses. E2 impacts the recruitment of immune cells to endothelium by regulating the expression of pattern recognition receptors. As endothelium is central to human physiology, it becomes a good target for many cancer and cardiovascular diseases. A broad range of genes get dysregulated during the course of pathophysiological events and many of them are regulated via E2 signalling. Recent evidence shows that E2 regulate the expression of many endothelial cell specific microRNAs (EC-miRNA), thereby affecting expression and stability of many factors including estrogen receptor alpha. In this study, we analysed two distinct datasets of different endothelial cell models to discern a set of genes that potentially play very crucial role in regulating general physiological as well as pathophysiological events. GEO2R and Cytoscape were used to analyze the datasets GSE51535 and GSE16683. DAVID and ClueGO functional annotation of the genes revealed association with genetically associated disease classes such as cancer and cardiovascular. KEGG pathways, Reactome pathways and Wiki-pathways were used for pathway enrichment analysis. One of the enriched pathways includes the synthesis of pri-miRNA by RNA polymerase II. Endothelial cell specific miRNA and target gene association revealed key miRNAs and their involvement in regulatory pathways. Overall, our study highlights the complexity of miRNA mediated E2 regulation of genes in endothelial cells and provides potential target genes for therapeutics in cancer and cardiovascular pathophysiological conditions.