Identification of potential molecular targets associated with proliferative diabetic retinopathy

Abstract

Background: This study aimed to identify and evaluate potential molecular targets associated with the development of proliferative diabetic retinopathy (DR). Methods: The microarray dataset "GSE60436" generated from fibrovascular membranes (FVMs) associated with proliferative DR was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) from the active FVMs and control or inactive FVMs and control were evaluated and co-DEGs were identified using VEEN analysis. Functional enrichment analysis, and protein-protein interactions (PPI) network and module analyses were performed on the upregulated and downregulated coDEGs. Finally, several predictions regarding microRNAs (miRNAs) and transcription factors (TFs) were made to construct a putative TF-miRNA-target network. Results: A total of 1475 co-DEGs were screened in active/inactive FVM samples, including 461 upregulated and 1014 downregulated genes, which were enriched for angiogenesis [Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Placental Growth Factor (PGF)] and visual perception, respectively. In the case of the upregulated co-DEGs, Kinesin Family Member 11 (KIF11), and BUB1 Mitotic Checkpoint Serine/Threonine Kinase (BUB1) exhibited the highest values in both the PPI network and module analyses, as well as the genes related to mitosis. In the case of downregulated co-DEGs, several G protein subunits, including G Protein Subunit Beta 3 (GNB3), exhibited the highest values in both the PPI network and module analyses. The genes identified in the module analysis were found to be from the signal transduction-related pathways. In addition, we were able to identify four miRNAs and five TFs, including miR-136 and miR-374. Conclusions: In brief, HIF1A, PGF, KIF11, G protein subunits, and miR-136, miR-374 may all be involved in angiogenesis, retinal endothelial cell proliferation, and visual signal transduction in proliferative DR. This study provides a number of novel insights that may aid the development of future studies dedicated to discovering novel therapeutic targets in proliferative DR.