To explore the role of hsa_circ_0053004/hsa-miR-646/CBX2 in diabetic retinopathy based on bioinformatics analysis and experimental verification

Abstract Objectives Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM), with a risk of blindness. The study was to search for effective biomarkers of DR. Methods The key molecules of DR were mined by bioinformatics. Dual luciferase reporter gene assay, knockdown and overexpression assay were used to detect the regulatory relationship between hsa_circ_0053004, hsa-miR-646, and CBX2 , and their clinical value was evaluated by constructing ROC curve. Levels of hsa_circ_0053004, hsa-miR-646, and CBX2 mRNA was detected by RT-qPCR, and western blotting was for detection of CBX2 protein expression. CCK-8 reagent and transwell assay were used for cell viability and migration detection. Results Hsa_circ_0053004 and CBX2 expressed highly in DR patients, while hsa-miR-646 was defective. Hsa_circ_0053004 down-regulated hsa-miR-646 by targeting it directly. Hsa-miR-646 inhibited CBX2 expression by targeting its 3′UTR. Overexpression of hsa_circ_0053004 or CBX2 promoted the high glucose-induced enhancement in human retinal microvascular endothelial cell (HRMEC) viability and migration, which was reversed by co-transfection of hsa-miR-646 mimic. The AUC of hsa_circ_0053004, hsa-miR-646, and CBX2 in predicting DR was 0.827, 0.805, and 0.817, respectively, and their combined AUC was 0.942. Conclusions Hsa_circ_0053004 promoted CBX2 expression by adsorbing hsa-miR-646, thereby promoting HRMECs to grow and migrate, and they may be good biomarkers of DR.