Differential expression profiling and functional prediction of circRNA in hypoxia-induced human retinal microvascular endothelial cells

Background Retinopathy of prematurity (ROP) is a severe retinal disorder primarily affecting premature infants, characterized by abnormal retinal blood vessel development. The pathogenesis of ROP is closely linked to hypoxic conditions, with human retinal microvascular endothelial cells (HRMECs) being particularly sensitive to hypoxia. Despite advancements in understanding ROP, the precise molecular mechanisms underlying its development remain poorly understood. Recent studies have identified the involvement of circular RNAs (circRNAs) in various human diseases, including retinal disorders, but their role in ROP remains unclear. Methods This study established a hypoxic cell model of ROP using HRMECs and analyzed the differential expression profiles of circRNAs induced by hypoxia using whole-transcriptome sequencing. Differentially expressed circRNAs (DE-circRNAs) were validated through qRT-PCR, and functional analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were conducted. Bioinformatics techniques were employed to construct circRNA-miRNA-mRNA regulatory networks. Results A total of 1,714 circRNAs were differentially expressed between normoxic and hypoxic groups, with 899 upregulated and 815 downregulated (fold-change ≥ 2, p ≤ 0.05). GO analysis revealed that DE-circRNAs were involved in various cellular processes, while KEGG analysis identified several associated pathways. CircRNA-miRNA-mRNA networks indicated that DE-circRNAs may contribute to ROP pathogenesis through the circRNA-targeted miRNA-mRNA axis. Conclusions This study identified the differential expression profile of circRNAs in the HRMEC hypoxia model. The findings suggest that the hsa_circ_0140253/hsa-miR-210-3p/ERFR and hsa_circ_0140253/hsa-miR-210-3p/PPARGC1A pathways are involved in ROP development via a sponge mechanism.