Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis via sponging microRNA-150

FASEB J. 2017 Oct;31(10):4472-4481. doi: 10.1096/fj.201700091R. Epub 2017 Jun 27.


The function of most human long noncoding RNAs (lncRNAs) remains unclear. Our studies identified a highly up-regulated mammalian lncRNA, FOXD3-AS1, known as linc1623 in mice, in the setting of hyperoxia/reactive oxygen species (ROS)-induced lung injury. We found that ROS induced a robust expression of FOXD3-AS1 in mouse lung tissue. Functionally, FOXD3-AS1 promoted oxidative stress-induced lung epithelial cell death. In human lung epithelial cells, the microRNA-150 (miR-150) was identified to interact with FOXD3-AS1; this finding was confirmed using the luciferase reporter assays. Consistently, mutation on the miR-150 pairing sequence in FOXD3-AS1 abolished the interactions between FOXD3-AS1 and miR-150. Additionally, miR-150 mimics suppressed the level of FOXD3-AS1. The antisense oligos of FOXD3-AS1 significantly augmented the intracellular level of miR-150, supporting the theory of sponging effects of FOXD3-AS1 on miR-150. We further investigated the cellular function of miR-150 in our lung injury models. MiR-150 conferred a cytoprotective role in lung epithelial cells after oxidative stress, whereas FOXD3-AS1 promoted cell death. Taken together, our studies indicated that FOXD3-AS1 serves as a sponge or as a competing endogenous noncoding RNA for miR-150, restricting its capability to promote cell growth and thereby exaggerating hyperoxia-induced lung epithelial cell death.-Zhang, D., Lee, H., Haspel, J. A., Jin, Y. Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis via sponging microRNA-150.

Keywords: epigenetic regulation; epithelial cell; hyperoxia; lncRNA array; lung injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Epithelial Cells / metabolism
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic
  • Lung Neoplasms / genetics
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Oxidative Stress* / genetics
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics*
  • Up-Regulation


  • Forkhead Transcription Factors
  • Foxd3 protein, mouse
  • MicroRNAs
  • Mirn150 microRNA, mouse
  • RNA, Long Noncoding
  • Repressor Proteins