Background: Asthma is a chronic respiratory disease characterised by the contraction of smooth muscle and remodelling of the airway wall, which is correlated with increased airway smooth muscle mass. Circular RNA (circRNA) circ_0002594 has been reported as a pro-inflammatory factor in allergic asthma. Therefore, this study is designed to explore the role and mechanism of circ_0002594 in human airway smooth muscle cells (HASMC) proliferation and metastasis.
Methods: Cell proliferative ability, invasion, and migration were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and Wound healing assays. The protein levels of E-cadherin, N-cadherin, and tripartite motif 8 (TRIM8) were detected by western blot assay. The levels of interleukin-6 (IL-6) and IL-13 were detected using Enzyme-linked immunosorbent assays (ELISA). Levels of circ_0002594, microRNA-139-5p (miR-139-5p), TRIM8 were determined by real-time quantitative polymerase chain reaction (RT-qPCR). The binding between miR-139-5p and circ_0002594 or TRIM8 was predicted by Circinteractome or Starbase v2.0, and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.
Results: Platelet-derived growth factor-BB (PDGF-BB) could trigger HASMC proliferation, metastasis, and inflammation. Circ_0002594 and TRIM8 were elevated in asthma patients and PDGF-BB-treated HASMC, and the miR-139-5p level was decreased. Furthermore, circ_0002594 knockdown could suppress PDGF-BB- stimulated HASMC damage. Mechanism analysis exhibited that circ_0002594 could regulate TRIM8 expression through sponging miR-139-5p.
Conclusion: Our findings revealed that circ_0002594 could act as a regulator in the airway remodelling during asthma development partly by the miR-139-5p/TRIM8 axis, hinting at an underlying therapeutic strategy for asthma.
Keywords: HASMC; TRIM8; asthma; circ_0002594; miR-139-5p.