Integrative analysis of miRNA–mRNA network in high altitude retinopathy by bioinformatics analysis

Abstract

Abstract High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA–mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA–mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.