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

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. FASEB J. 31, 4472–4481 (2017). www.fasebj.org