LncRNA NEAT1 regulates MMP-16 by targeting miR-200a/b to aggravate inflammation in asthma

Abstract

Asthma is a common respiratory disease which is characterized by persistent airway inflammation. Abnormal expression of long non-coding RNAs (lncRNAs) is observed in asthma. However, whether lncRNA nuclear-enriched abundant transcript 1 (NEAT1) regulates asthmatic inflammation and its mechanism still needs to be further investigated. The expression levels of inflammatory factors (tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-13, and IL-10) were detected using reverse transcription quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). MTT and flow cytometry assays were employed to determine cell proliferation and apoptosis, respectively. Dual luciferase reporter assay was performed to verify the relationship between miR-200a/b and MMP-16 or NEAT1. NEAT1 silencing markedly reduced TNF-α, IL-4, and IL-13 levels, while elevated IL-10 expression, suppressed cell proliferation, and promoted cell apoptosis. However, NEAT1 overexpression elicited the opposite effects on cell proliferation and inflammation cytokines secretion. What is more, NEAT1 negatively regulated miR-200a/b expression, and MMP16 was a target gene of miR-200a/b. miR-200a/b overexpression suppressed inflammation, cell proliferation, and enhanced cell apoptosis through regulation of MMP16. Moreover, MMP-16 overexpression or miR-200a/b inhibition abolished the regulatory effect of sh-NEAT1 on cell inflammation and apoptosis in BEAS-2B cells. NEAT1 acted as the role of sponge for miR-200a/b to regulate MMP-16 expression, thereby promoting asthma progression, suggesting that NEAT1 might have great potential as therapeutic target for asthma.

Keywords:

• lncRNA NEAT1
• miR-200a/b
• MMP-16
• asthma
• airway inflammation

Acknowledgements

The authors sincere gratitude to the reviewers for their constructive comments.

Author contributions

XJD: conceptualization; funding acquisition; XZ: writing-original draft; data curation; resources; ND: methodology; formal analysis; JYZ: investigation; software; visualization; YPC: project administration; supervision; validation; writing-review and editing. All authors have read and approved the final version of this manuscript to be published.

Disclosure statement

The authors declare that there is no conflict of interest.

Data availability statement

All data generated or analysed during this study are included in this article. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Clinical Medical Innovation Guidance Project of Hunan Provincial Science and Technology Department under Grant Number [2018SK50406].