Zhang Duo, Lee Heedoo, Haspel Jeffrey A, Jin Yang
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, Massachusetts, USA.
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
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, , known as in mice, in the setting of hyperoxia/reactive oxygen species (ROS)-induced lung injury. We found that ROS induced a robust expression of FOXD3 in mouse lung tissue. Functionally, promoted oxidative stress-induced lung epithelial cell death. In human lung epithelial cells, the microRNA-150 (miR-150) was identified to interact with ; 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 sponging microRNA-150.
大多数人类长链非编码RNA（lncRNA）的功能仍不清楚。我们的研究在高氧/活性氧（ROS）诱导的肺损伤背景下，鉴定出一种在哺乳动物中高度上调的lncRNA，在小鼠中称为 。我们发现ROS可诱导小鼠肺组织中FOXD3的强烈表达。在功能上， 促进氧化应激诱导的肺上皮细胞死亡。在人肺上皮细胞中，已鉴定出微小RNA-150（miR-150）与 相互作用；使用荧光素酶报告基因检测证实了这一发现。一致地，FOXD3-AS1中miR-150配对序列上的突变消除了FOXD3-AS1与miR-150之间的相互作用。此外，miR-150模拟物可抑制FOXD3-AS1的水平。FOXD3-AS1的反义寡核苷酸显著提高了细胞内miR-150的水平，支持了FOXD3-AS1对miR-150的海绵效应理论。我们进一步研究了miR-150在我们的肺损伤模型中的细胞功能。在氧化应激后，miR-150在肺上皮细胞中发挥细胞保护作用，而FOXD3-AS1则促进细胞死亡。综上所述，我们的研究表明，FOXD3-AS1作为miR-150的海绵或竞争性内源性非编码RNA，限制了其促进细胞生长的能力，从而加剧了高氧诱导的肺上皮细胞死亡。-张，D.，李，H.，哈斯佩尔，J.A.，金，Y.长链非编码RNA FOXD3-AS1通过海绵化微小RNA-150调节氧化应激诱导的细胞凋亡
