RESULTS: Transcriptomic profiles in the pulmonary arteries of HPH rats were characterized through high-throughput
RNA sequencing in this study. Through relatively strict screening, a set of differentially expressed RNAs (DERNAs) including 19 DEmRNAs, 8 DElncRNAs, 19 DEcircRNAs, and 23 DEmiRNAs were identified between HPH and normal rats. The DEmRNAs were further found to be involved in cell adhesion, axon guidance,
PPAR signaling pathway, and calcium signaling pathway, suggesting their crucial role in HPH. Moreover, a
hypoxia-induced
ceRNA regulatory network in the pulmonary arteries of HPH rats was constructed according to the
ceRNA hypothesis. More specifically, the
ceRNA network was composed of 10
miRNAs as hub nodes, which might be sponged by 6
circRNAs and 7 lncRNAs, and directed the expression of 18 downstream target genes that might play important role in the progression of HPH. The expression patterns of selected DERNAs in the
ceRNA network were then validated to be consistent with sequencing results in another three independent batches of HPH and normal control rats. The diagnostic effectiveness of several hub mRNAs in
ceRNA network was further evaluated through investigating their expression profiles in patients with pulmonary artery
hypertension (PAH) recorded in the Gene Expression Omnibus (GEO) dataset GSE117261. Dysregulated POSTN, LTBP2, SPP1, and LSAMP were observed in both the pulmonary arteries of HPH rats and lung tissues of PAH patients.
CONCLUSIONS: A
ceRNA regulatory network in the pulmonary arteries of HPH rats was constructed, 10 hub
miRNAs and their corresponding interacting lncRNAs,
circRNAs, and mRNAs were identified. The expression patterns of selected DERNAs were further validated to be consistent with the sequencing result. POSTN, LTBP2, SPP1, and LSAMP were suggested to be potential diagnostic
biomarkers and therapeutic targets for PAH.