LncRNA-N1LR Enhances Neuroprotection Against Ischemic Stroke Probably by Inhibiting p53 Phosphorylation (original) (raw)

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.

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Acknowledgments

We thank the Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation for flow cytometry support. This work was supported by the National Nature Science Foundation of China grant NSFC81370449.

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Authors and Affiliations

  1. Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Industrial avenue253, Guangzhou, 510282, China
    Zhuomin Wu, Yixin Qin, Qian Xu, Shuai He, Bohong Cen, Wenjie Liao & Aimin Ji
  2. Pharmacy Department, Chengdu First People’s Hospital/ Chengdu Integrated TCM & Western Medicine Hospital, Chengdu, China
    Ping Wu
  3. Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
    Xialin Zuo
  4. The Second Clinical College of Southern Medical University, Guangzhou, China
    Na Yu

Authors

  1. Zhuomin Wu
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  2. Ping Wu
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  3. Xialin Zuo
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  4. Na Yu
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  5. Yixin Qin
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  6. Qian Xu
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  7. Shuai He
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  8. Bohong Cen
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  9. Wenjie Liao
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  10. Aimin Ji
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Correspondence toAimin Ji.

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The authors declare that they have no conflict of interest.

Additional information

Zhuomin Wu and Ping Wu contributed equally to this work.

An erratum to this article is available at https://doi.org/10.1007/s12035-016-0354-9.

Electronic supplementary material

Table S1

Sequences of primers and siRNA used in this study. (DOCX 19 kb)

Table S2

Differentially expressed lncRNAs identified in ischemic penumbra tissue. (PDF 490 kb)

Table S3

Differentially expressed mRNAs identified in ischemic penumbra tissue. (PDF 787 kb)

Table S4

The functions of mRNAs up-regulated over 100 fold-changes in ischemic penumbra. (PDF 221 kb)

Table S5

Functions of genes connected to lncRNA-N1LR in sub-network. (PDF 48 kb)

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Wu, Z., Wu, P., Zuo, X. et al. LncRNA-N1LR Enhances Neuroprotection Against Ischemic Stroke Probably by Inhibiting p53 Phosphorylation.Mol Neurobiol 54, 7670–7685 (2017). https://doi.org/10.1007/s12035-016-0246-z

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