Regulation Network Analysis Of Let-7e Impacting On Endothelial Cell Function

Objective:This study was aimed to analysis the difference expression of mRNA and lncRNAs under the influence of let-7e in the endothelial cells by mRNA and lncRNA microarray technology. We sought significant differential expressed lncRNAs and mRNA by bioinformatics method and identified co-expression genes of differential lncRNA through functional clustering of mRNA, predicted biological function of lncRNA and signaling pathways involved in, constructed lncRNA-let-7e-mRNA interaction networks. This study will support the foundation theory for the role of let-7e of endothelial cells.Method:1. Culturing Human Umbilical Vein Endothelial Cells(HUVECs) and divided them into 6 groups, transfecting let-7e mimic、let-7e inhibitor and negative Control and then extracting total RNA.2. We applied the DAVID and WEB-based Gene Set Analysis Toolkit software for differentially expressed mRNA to analyze gene cluster function and obtain signaling pathways and biological functions of mRNA; prediced differentially expressed genes of lncRNA and their co-expression function by pearson correlation coefficient, constructed lncRNA-let-7e-mRNA interaction networks by Cytoscape.Result:1. The differently analysis of microarray revealed that comparison between inhibitor and the negative control group, differently expressed lncRNAs were detected as follows(difference ratio>2, p<0.05):total of 1126 different lncRNAs were detected, total of 942mRNAs were detected; comparison between mimic and the negative control group, total of 819 lncRNAs were detected, total of 621 mRNAs were detected.2. We found the co-expression pair of mRNA-lncRNA by co-expression of cluster analysis and functional cluster analysis of mRNA, then found 7 let-7e bindingsites and regulatory pathways that let-7e acting on endothelial cells.Conclusion:We found that let-7e is closely related to many biological processes of HUVECs, such as inflammatory response, cell proliferation, apoptosis and lipid metabolism. Through building lncRNA-let-7e-mRNA interaction networks and predicting biological function of the essential nodes lncRNA, we found that the CeRNA network with the core of let-7e and is closely related to inflammation of HUVECs, forming a pro-inflammatory regulatory network to play an important role in the ox-LDL induced inflammation of HUVECs.