Circ-BPTF Associated Pulmonary Vascular Remodeling in COPD Via Promoting Smooth Muscle Cells Proliferation by MiR-486-5p/CEMIP Axis

Background As a kind of non-coding RNA, circle RNA has been proved acting critical role in multiple diseases, including pulmonary hypertension. In this study, we investigated the role of a novel circRNA circ-BPTF, miR-486-5p and the downstream targets in pulmonary vascular remodeling of chronic obstructive pulmonary disease (COPD) patients. Methods A circRNA microarray was firstly used for circRNAs involved in pulmonary vascular remodeling of COPD patients. Real-time PCR and western blot analysis were performed to identify circ-BPTF, miR-486-5p and cell migration-inducing protein (CEMIP) expression. CCK-8, immunofluorescence and luciferase assay were used for exploring the role of circ-BPTF in proliferation. Results The circRNA microarray and real-time PCR analysis showed significant higher levels of circ-BPTF and lower miR-486-5p levels in pulmonary vessels of COPD patients. Hypoxia suppressed miR-486-5p expression but promoted expression of circ-BPTF and CEMIP in human pulmonary arterial smooth muscle cells (PASMCs) in vitro. The loss-of-function and gain-of-function experiments showed that circ-BPTF promoted PASMCs proliferation in vitro. Moreover, luciferase assay results indicated that circ-BPTF regulated proliferation by acting as an miR-486-5p sponge. CEMIP was identified as candidate target genes of miR-486-5p by luciferase assay. Conclusion Summarily, our study showed that circ-BPTF was associated with pulmonary vascular remodeling of COPD via promoting smooth muscle cells proliferation by miR-486-5p regulating CEMIP pathway.