Circular RNA circ_0002594 regulates PDGF-BB-induced proliferation and migration of human airway smooth muscle cells via sponging miR-139-5p/TRIM8 in asthma

Abstract

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:

• circ_0002594
• miR-139-5p
• TRIM8
• asthma
• HASMC

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability statement

All data generated or analysed during this study are included in this article.

Additional information

Funding

This study was supported by the Analysis of quality of life in children and adolescents with bronchial asthma in Qinhuangdao.