Abstract
BACKGROUND: Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. METHODS: Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real-time polymerase chain reaction, Cell Counting Kit-8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. RESULTS: PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA-432-5p (miR-432-5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR-433-3p in PMECs, and upregulate zinc finger AN1-type containing 5 (ZFAND5) expression by targeting miR-3613-5p in PCs. CONCLUSIONS: Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs, through the miR-433-3p/MXI1 axis in PMECs, and through the miR-3613-5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.