Circular RNA ERBB2 Contributes to Proliferation and Migration of Airway Smooth Muscle Cells via miR-98-5p/IGF1R Signaling in Asthma

Jun-Qian Huang,1 Fang Wang,2 Long-Tao Wang,3 Yong-Mei Li,4 Jun-Li Lu,5 Jian-You Chen2 1Department of Respiratory and Critical Medicine, Qingdao Chengyang District People’s Hospital, Qingdao, Shandong, People’s Republic of China; 2Department of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Critical Care Medicine, Qingdao Chengyang District People’s Hospital, Qingdao, Shandong, People’s Republic of China; 4Department of Clinical Pharmacy, Qingdao Chengyang District People’s Hospital, Qingdao, Shandong, People’s Republic of China; 5Qingdao Chengyang District People’s Hospital, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Jian-You ChenDepartment of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of ChinaEmail youchanmou9834@163.comBackground: 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