Identification Of Platelet-related Biomarkers And Construction of Transcriptional Regulatory Network in Patients with Proliferative Diabetic Retinopathy

Abstract

Abstract Objective: To identify the platelet-related biomarkers in Proliferative diabetic retinopathy (PDR). Methods: Two mRNA expression profiles of PDR (GSE102485 and GSE60436) were downloaded from the Gene Expression Omnibus (GEO) database with the platelet-related genes from gene set enrichment analysis (GSEA) database. A protein-protein interaction (PPI) network was established to screen out hub genes based on the interaction between differentially expressed platelet-related genes (DEPRGs), followed by the prediction of the associated microRNAs (miRNAs), transcription factors (TFs) and drugs, which were taken to establish the regulatory networks of miRNA-hub gene, TF-hub gene and drug-hub gene. To verify the expression of Hub genes, both retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) were subjected to quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: A total of 168 DEPRGs were determined, with 146 genes for upregulation and 22 for downregulation. 9 hub genes (CDC42, GNAI2, LCK, LCP2, LYN, PLCG2, PTPN6, RAC1 and SYK) were eventually screened. 446 miRNAs, 46 TFs and 138 hub gene targeted by drugs were presented after prediction. RAC1 and GNAI2 respectively targeted by 156 miRNAs and 19 TFs lied the most connected hub genes in the miRNA-hub gene and TF-hub gene regulatory networks. Based on the drug-hub gene regulatory network, LCK was targeted by 52 drugs. qRT-PCR results indicated that the expression of LPC2 and PTPN6 was upregulated in both diabetes mouse models and HRMECs treated with HG. Conclusions: Nine hub genes were screened with the prediction of miRNAs, which were targeted by TFs and drugs, and may play an essential role in the progression of PDR, utilized as potential biomarkers and therapeutic targets.