Characteristics of circular RNA expression in lung tissues from mice with hypoxia-induced pulmonary hypertension

摘要

Pulmonary hypertension (PH) is a life-threatening lung disease, characterized by an increase in pulmonary arterial pressure caused by vasoconstriction and vascular remodeling. The pathogenesis of PH is not fully understood, and there is a lack of potential biomarkers for the diagnosis and treatment of patients with PH. Non-coding RNAs with a characteristic covalently closed loop structure, termed circular RNAs (circRNAs), are present in a number of pulmonary diseases. To the best of our knowledge, the present study is the first to use microarray analysis to determine the expression profile of circRNAs in lung tissues from mice with hypoxia-induced PH. In total, 23 significantly upregulated and 41 significantly down-regulated circRNAs were identified. Of these, 12 differentially expressed circRNAs were selected for further validation using reverse transcription-quantitative polymerase chain reaction. Putative microRNAs (miRNAs) that bind to the dysregulated circRNAs were predicted. Subsequently, bioinformatics tools were used to construct circRNA-miRNA-mRNA networks for the two most promising circRNAs, namely mmu_circRNA_004592 and mmu_circRNA_018351. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target genes of the dysregulated circRNAs revealed that these dysregulated circRNAs may serve an important role in the pathogenesis of hypoxia-induced PH. Therefore, these dysregulated circRNAs are candidate diagnostic biomarkers and potential therapeutic targets for PH.