Constructing microRNA-mRNA Integrative Network of miR-204-5p and miR-211-5p in RPE Cells Going Through EMT

Abstract

Aims: The retinal pigment epithelium cells (RPE) have crucial roles in the health and functionality of retina. Any damage or dysfunction of these cells can lead to severe retinopathies. Identification of signaling pathways and biological processes involved in RPE differentiation can be useful in devising more robust therapeutic approaches. Materials and Methods: In the present study, we used the intersection of three online prediction databases and their ::union:: with one experimental database to select microRNAs gene targets. Next, by the intersect of the targeted genes with an increase in their expression in epithelial to mesenchymal transition (EMT) of RPE cells, we tried to build a microRNA-mRNA integrative network. Further, several pathway analyses tools were used to perform a more accurate and comprehensive analysis of the signaling pathways and biological processes being regulated by selected miRs in the EMT of the RPE cells. Findings: Our study revealed that among the 3406 genes being upregulated over the course of EMT in RPE cells, adj p-value≤0.05, fold change≥1.5, 93 genes were miR-204-5p and miR 211-5p target genes. Further analysis of the obtained target gene list demonstrated that these two microRNAs are mostly involved in maintaining RPE cells from going through EMT via regulation of cell adhesion and secretion subnetworks and also MAPK and TGF-β1 signaling pathways while preserving cells from apoptosis and neuronal fates. Conclusion: This study indicated that miR-204-5p and miR 211-5p are involved in protecting RPE cells from EMT and reinforce their epithelial cell identity.