Long non-coding RNA TUG1 accelerates abnormal growth of airway smooth muscle cells in asthma by targeting the miR-138-5p/E2F3 axis

Asthma is a chronic airway inflammatory disease. The present study aimed to explore the effect of the long non-coding RNA taurine-upregulated gene 1 (TUG1) on the viability and migration of airway smooth muscle cells (ASMCs) in asthma. Rat asthma models were constructed with ovalbumin sensitization and challenge and the level of serum immunoglobulin E (IgE) and the rates of inspiratory and expiratory resistance were measured. Reverse transcription-quantitative PCR was also performed to determine the expression levels of TUG1. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were then used as a cell model of asthma. The viability and migratory abilities of ASMCs were analysed with the MTT and Transwell assays. Additionally, a dual-luciferase reporter assay was used to confirm the relationship between TUG1 and microRNA (miR)-138-5p and between transcription factor E2F3 and miR-138-5p. The expression of TUG1, level of serum IgE, inspiratory resistance and expiratory resistance were clearly increased in the rat asthma model in comparison with controls. Knockdown of TUG1 the viability and migration of PDGF-BB-induced ASMCs and reduced the inspiratory and expiratory resistances. In addition, TUG1 functioned as a bait of miR-138-5p, and miR-138-5p modulated E2F3 expression. Knockdown of E2F3 hindered the abnormal growth of ASMCs. Moreover, miR-138-5p inhibition or E2F3 overexpression reversed the inhibitory effects of TUG1 knockdown on viability and migration of PDGF-BB-induced ASMCs. The TUG1/miR-138-5p/E2F3 regulatory axis appeared to play a critical role in accelerating the viability and migration of ASMCs and may therefore have a role in asthma.

Automated summary

This study found that upregulation of TUG1 in asthma models increased survival and migration of ASMCs, as well as respiratory resistance. Knockdown of TUG1 reduced these effects and modulated ASMCs proliferation and migration through miR-138-5p and E2F3 pathways.