LncRNA UCA1 remits LPS-engendered inflammatory damage through deactivation of miR-499b-5p/TLR4 axis

IUBMB Life. 2021 Feb;73(2):463-473. doi: 10.1002/iub.2443. Epub 2020 Dec 31.

Abstract

Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPS-injured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1β, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPS-stimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.

Keywords: apoptosis; inflammatory damage; lncRNA UCA1; miR-499b-5p/TLR4 axis; pneumonia.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblasts / drug effects*
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Lipopolysaccharides / adverse effects*
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • RNA, Long Noncoding / genetics*
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Lipopolysaccharides
  • MIRN499 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • UCA1 RNA, human