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

• Published in: Molecular neurobiology 2017-12, Vol.54 (10), p.7670-7685
• Main Authors: Wu, Zhuomin, Wu, Ping, Zuo, Xialin, Yu, Na, Qin, Yixin, Xu, Qian, He, Shuai, Cen, Bohong, Liao, Wenjie, Ji, Aimin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Base Sequence; Biomedical and Life Sciences; Biomedicine; Brain injury; Brain Ischemia - genetics; Brain Ischemia - metabolism; Brain Ischemia - prevention & control; Cell Biology; Cell cycle; Cell proliferation; DNA microarrays; Gene expression; Genomes; Glucose; Injury analysis; Ischemia; Male; Mice; Mice, Inbred C57BL; mRNA; Neurobiology; Neurology; Neuroprotection; Neuroprotection - physiology; Neurosciences; Oxygen; p53 Protein; Phosphorylation; Phosphorylation - physiology; Rats; Rats, Sprague-Dawley; Reperfusion; RNA, Long Noncoding - biosynthesis; RNA, Long Noncoding - genetics; Serine; Stroke; Stroke - genetics; Stroke - metabolism; Stroke - prevention & control; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-0246-z

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.