LncRNA NEAT1 promotes airway smooth muscle cell inflammation by activating the JAK3/STAT5 pathway through targeting of miR-139

Abstract

Background Asthma is a chronic inflammatory heterogeneous respiratory disease. Previous studies showed that the lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1) might play an important role in the pathogenesis of asthma, but its potential mechanism in airway smooth muscle cell (ASMC) inflammation remains largely unknown and needs further investigation.

Methods We performed cellular immunofluorescence to identify the features of ASMCs and detected the expression levels of lncRNA NEAT1, miR-139, TNF-α, IL-6, IL-8 and IL-1β by quantitative real-time PCR (Q-PCR) and ELISA. Western blotting (WB) was used to measure the protein expression of the related genes, and bioinformatics as well as dual luciferase assays were used to validate the interaction between lncRNA NEAT1 and miR-139 and the interaction between miR-139 and the 3’-UTR of JAK3.

Results The expression of lncRNA NEAT1 was increased in the ASMCs of asthma patients, but miR-139 was decreased. Overexpression of lncRNA NEAT1 promoted the expression of the inflammatory cytokines such as TNF-α, IL-6, IL-8 and IL-1β in ASMCs. LncRNA NEAT1 was able to target miR-139 to activate the JAK3/STAT5 signaling pathway and induced the expression of these inflammatory cytokines in ASMCs. Overexpression of miR-139 or suppression of the JAK3/STAT5 signaling pathway reversed the inflammatory effect of lncRNA NEAT1.

Conclusion LncRNA NEAT1 played a pivotal role in ASMC inflammation and exerted its function through the miR-139/JAK3/STAT5 signaling network.

Keywords:

• ASMCs
• inflammation
• JAK3/STAT5 pathway
• LncRNA NEAT1
• miR-139

Conflict of interests

The authors declare that they have no conflict of interest.

Additional information

Funding

This work is supported by Hainan Provincial Key Research and Development Program (No. ZDYF2018150); National Natural Science Foundation of China (No. 81860007)；Basic and Applied Research Project of Hainan Province (No.2019RC372).