circ_CSNK1E modulates airway smooth muscle cells proliferation and migration via miR-34a-5p/VAMP2 axis in asthma.

BACKGROUND: Excessive proliferation and migration of airway smooth muscle cells (ASMCs) directly lead to airway remodeling in asthma. However, the role of circular RNAs (circRNAs) in airway remodeling remains unclear. This study aimed to investigate the regulatory role and mechanism of circ_CSNK1E in ASMCs proliferation and migration. METHODS: In this study, RNA-sequencing was used to analyze cicRNAs expression in asthma samples. ASMCs were treated with 25 ng/ml PDGF-BB to establish a model of asthma in vitro. Then, we used RT-qPCR to assess circRNAs, microRNAs (miRNAs) and messenger RNAs (mRNAs) expression. Besides, CCK-8, colony formation, wound healing and transwell chamber assays were carried out to explore cell proliferation and migration. Subcellular localization assay was used to detect the location of circRNA. Next, bioinformatics, luciferase reporter and RIP assays were performed to evaluate the relationship among circ_CSNK1E, miRNA-34a-5p and VAMP2. RESULTS: circ_CSNK1E expression was found to be significantly up-regulated in asthma samples and PDGF-BB-induced ASMCs. Functional experiments revealed that inhibition of circRNA_CSNK1E suppressed proliferation and migration of ASMCs stimulated by PDGF-BB. Next, we found that circRNA_CSNK1E served as a sponge for miR-34a-5p in ASMCs, and miR-34a-5p mimic suppressed proliferation and migration of ASMCs. Moreover, VAMP2 was confirmed as a direct target of miR-34a-5p. At last, inhibition of circRNA_CSNK1E suppressed proliferation and migration of ASMCs stimulated by PDGF-BB through miR-34a-5p/VAMP2 axis. CONCLUSION: Collectively, these findings clarified the importance of circ_CSNK1E/miRNA-34a-5p/VAMP2 axis for the proliferation and migration of ASMCs. These indicated that inhibition of circ_CSNK1E might be a potential target for the treatment of airway remodeling in asthma.