Research Paper Advance Articles

Silencing of long non-coding RNA MEG3 alleviates lipopolysaccharide-induced acute lung injury by acting as a molecular sponge of microRNA-7b to modulate NLRP3

Handi Liao1, *, , Suning Zhang2, *, , Jianou Qiao3, ,

  • 1 Department of Intensive Care Unit, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201999, P.R. China
  • 2 Department of Emergency Medicine, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201999, P.R. China
  • 3 Department of Respiratory Medicine, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, P.R. China
* Co-first authors

Received: December 4, 2019       Accepted: March 30, 2020       Published: August 27, 2020      

https://doi.org/10.18632/aging.103752
How to Cite

Copyright © 2020 Liao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cited.

Abstract

We aimed to elucidate the roles of the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3)/microRNA-7b (miR-7b)/NLR pyrin domain containing 3 (NLRP3) axis in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Mouse alveolar macrophage NR8383 and mice were administrated with LPS to establish ALI models in vitro and in vivo. NLRP3 was silenced while miR-7b was overexpressed in LPS-induced NR8383 cell model of ALI. The interleukin-18 (IL-18) and IL-1β, as well as caspase-1, tumor necrosis factor-α (TNF-α) and IL-6 protein levels were assayed. To further investigate the underlying mechanisms of NLRP3 in ALI, lncRNA MEG3 was silenced and miR-7b was overexpressed in LPS-induced NR8383 cell model of ALI, after which in vivo experiments were performed for further verification. NLRP3 was highly expressed in LPS-induced NR8383 cell model of ALI. Silencing NLRP3 or overexpressing miR-7b inhibited IL-18 and IL-1β, as well as caspase-1, TNF-α and IL-6. LncRNA MEG3 could sponge miR-7b, and lncRNA MEG3 silencing or miR-7b overexpression downregulates NLRP3 expression, thus reducing IL-18 and IL-1β, as well as caspase-1, TNF-α and IL-6 levels. The in vivo experiments further confirmed the aforementioned findings. Silencing lncRNA MEG3 augments miR-7b binding to NLRP3 and downregulates NLRP3 expression, which ultimately improves LPS-induced ALI.

Abbreviations

ALI: acute lung injury; LPS: lipopolysaccharide; NLRs: nod-like receptors; DAMPs: danger-associated molecular patterns; FBS: fetal bovine serum; SPF: specific pathogen free.