title: LncRNA-N1LR Enhances Neuroprotection Against Ischemic Stroke Probably by Inhibiting p53 Phosphorylation.
abstract: 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.
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China.
authors.forename: Zhuomin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Pharmacy Department, Chengdu First People's Hospital/ Chengdu Integrated TCM & Western Medicine Hospital, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Xialin
authors.initials: X
authors.lastname: Zuo
authors.affiliation: The Second Clinical College of Southern Medical University, Guangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: He
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China.
authors.forename: Bohong
authors.initials: B
authors.lastname: Cen
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Liao
authors.affiliation: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China. aiminji_007@163.com.
authors.forename: Aimin
authors.initials: A
authors.lastname: Ji
mesh_terms: D000818:Animals; D001483:Base Sequence; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000066829:Neuroprotection / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; Cell proliferation; Ischemic stroke; Neuroprotection; lncRNA-N1LR; p53