Abstract
Noncoding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). In this study, we investigated the roles of hsa_circ_0016070, miR-942, and CCND1 in PAH. circRNA microarray was used to search circRNAs involved in PAH, whereas real-time PCR and western blot analysis were performed to detect miR-942 and CCND1 expression in different groups. In addition, the effect of miR-942 on CCND1 expression, as well as the effect of hsa_circ_0016070 on the expression of miR-942 and CCND1, was also studied using real-time PCR and western blot analysis. Moreover, MTT assay and flow cytometry were used to detect the effect of hsa _circ_0016070 on cell proliferation and cell cycle. According to the results of circRNA microarray analysis, hsa _circ_0016070 was identified to be associated with the risk of PAH in chronic obstructive pulmonary disease (COPD) patients. The miR-942 level in the COPD(+) PAH(+) group was much lower than that in the COPD(+) PAH(-) group, while the CCND1 level in the COPD(+) PAH(+) group was much higher. CCND1 was identified as a candidate target gene of miR-942, and the luciferase assay showed that the luciferase activity of wild-type CCND1 3' UTR was inhibited by miR-942 mimics. In addition, hsa _circ_0016070 reduced miR-942 expression and enhanced CCND1 expression. Furthermore, hsa _circ_0016070 evidently increased cell viability and decreased the number of cells arrested in the G1/G0 phase. In summary, the results of this study suggested that hsa_circ_0016070 was associated with vascular remodeling in PAH by promoting the proliferation of pulmonary artery smooth muscle cells (PASMCs) via the miR-942/CCND1. Accordingly, has_circ_0016070 might be used as a novel biomarker in the diagnosis and treatment of PAH.