Background: Asthma belongs to chronic inflammatory respiratory diseases characterized by airway inflammation and remodeling. Circular RNAs (circRNAs) are promising therapeutic targets for various diseases, including asthma. In this work, we aim to investigate the role of circular RNA Erb-B2 receptor tyrosine kinase 2 (circERBB2) during progression of asthma.
Methods: Human airway smooth muscle cells (ASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) to mimic cell remodeling. The expression of circERBB2, microRNA-98-5p (miR-98-5p) , and insulin-like growth factor 1 receptor (IGF1R)  was measured by qRT-PCR. Cell proliferation, migration and apoptosis were determined by cell counting-8 (CCK-8), transwell, and flow cytometry. Protein levels of PCNA, MMP-9, IGF1R were evaluated using Western blotting. The levels of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 were detected by enzyme‐linked immunosorbent assay (ELISA). Luciferase reporter gene experiment was adopted to evaluate the targeting relationship between miR-98-5p  with circERBB2  and IGF1R . Interaction between RNAs was determined by RNA pulldown and RIP assay.
Results: The depletion of circERBB2  attenuated the proliferation, migration, and levels of inflammatory factors induced by PDGF-BB and cell apoptosis. CircERBB2  was identified to directly interact with miR-98-5P , and overexpression of miR-98-5p  abolished the function of circERBB2  on PDGF-BB-stimulated ASMCs. IGF1R  was identified as a target of miR-98-5p , and knockdown of IGF1R  relieved the PDGF-BB-induced ASMCs proliferation and migration.
Conclusion: Our work disclosed that knockdown of circERBB2 suppressed PDGF-BB-caused proliferation, migration and inflammatory response of ASMCs, through regulating miR-98-5p/IGF1R signaling, presented circERBB2 as a promising therapeutic target for asthma.
Keywords: asthma, circERBB2, miR-98-5p, IGF1R, proliferation, migration