LncRNA-N1LR Enhances Neuroprotection Against Ischemic Stroke Probably by Inhibiting p53 Phosphorylation

Mol Neurobiol. 2017 Dec;54(10):7670-7685. doi: 10.1007/s12035-016-0246-z. Epub 2016 Nov 14.


In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical roles in a broad range of cell biological processes. However, the activities of lncRNAs during ischemic stroke remain largely unknown. In this study, we carried out a genome-wide lncRNA microarray analysis in rat brains with ischemia/reperfusion (I/R) injury. The results revealed the differential expression of a subset of lncRNAs. Through the construction of lncRNA-mRNA co-expression networks, we identified lncRNA-N1LR as a novel I/R-induced lncRNA. The functions of lncRNA-N1LR were assessed by silencing and overexpressing this lncRNA in vitro and in vivo. We found that lncRNA-N1LR enhanced cell cycle progression and cell proliferation, and inhibited apoptosis in N2a cells subjected to in vitro ischemia (oxygen-glucose deprivation/reoxygenation, OGD/R). Furthermore, we showed that lncRNA-N1LR reduced neuronal apoptosis and neural cell loss in I/R-induced mouse brains. Mechanistically, we discovered that lncRNA-N1LR promoted neuroprotection probably through the inhibition of p53 phosphorylation on serine 15 in a manner that was independent of its location-associated gene Nck1. In summary, our results indicated that lncRNA-N1LR promoted neuroprotection against ischemic stroke probably by inactivating p53. Thus, we propose that lncRNA-N1LR may serve as a potential target for therapeutic intervention following ischemic brain injury.

Keywords: Apoptosis; Cell proliferation; Ischemic stroke; Neuroprotection; lncRNA-N1LR; p53.

MeSH terms

  • Animals
  • Base Sequence
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Brain Ischemia / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotection / physiology
  • Phosphorylation / physiology
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Stroke / genetics
  • Stroke / metabolism*
  • Stroke / prevention & control*
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53