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Journal of Molecular Neuroscience

, Volume 58, Issue 4, pp 507–516 | Cite as

MicroRNA-25 Negatively Regulates Cerebral Ischemia/Reperfusion Injury-Induced Cell Apoptosis Through Fas/FasL Pathway

  • Jun-feng Zhang
  • Li-li Shi
  • Li Zhang
  • Zhao-hua Zhao
  • Fei Liang
  • Xi XuEmail author
  • Ling-yu ZhaoEmail author
  • Peng-bo Yang
  • Jian-shui Zhang
  • Ying-fang Tian
Article

Abstract

MicroRNA-25 (miR-25) has been reported to be a major miRNA marker in neural cells and is strongly expressed in ischemic brain tissues. However, the precise mechanism and effect of miR-25 in cerebral ischemia/reperfusion (I/R) injury needs further investigations. In the present study, the oxygen-glucose deprivation (OGD) model was constructed in human SH-SY5Y and IMR-32 cells to mimic I/R injury and to evaluate the role of miR-25 in regulating OGD/reperfusion (OGDR)-induced cell apoptosis. We found that miR-25 was downregulated in the OGDR model. Overexpression of miR-25 via miRNA-mimics transfection remarkably inhibited OGDR-induced cell apoptosis. Moreover, Fas was predicted as a target gene of miR-25 through bioinformatic analysis. The interaction between miR-25 and 3′-untranslated region (UTR) of Fas mRNA was confirmed by dual-luciferase reporter assay. Fas protein expression was downregulated by miR-25 overexpression in OGDR model. Subsequently, the small interfering RNA (siRNA)-mediated knockdown of Fas expression also inhibited cell apoptosis induced by OGDR model; in contrast, Fas overexpression abrogated the protective effects of miR-25 on OGDR-induced cells. Taken together, our results indicate that the upregulation of miR-25 inhibits cerebral I/R injury-induced apoptosis through downregulating Fas/FasL, which will provide a promising therapeutic target.

Keywords

microRNA-25 Ischemia/reperfusion injury Apoptosis Fas/FasL 

Abbreviations

OGD

Oxygen-glucose deprivation

OGDR

Oxygen-glucose deprivation/reperfusion

UTR

Untranslated region

miR-25

microRNA-25

Notes

Acknowledgments

This research was funded by the National Natural Science Foundation of China (No.81301041, No.31371501), the Scientific Research Program Funded by the Department of Science and Technology of Shaanxi Province (No.2015KJXX-43, 2014JM4096), and the Leading Disciplines Development Government Foundation of Shaanxi, China (No. [2014]3-1001).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jun-feng Zhang
    • 1
  • Li-li Shi
    • 1
  • Li Zhang
    • 1
  • Zhao-hua Zhao
    • 1
  • Fei Liang
    • 1
  • Xi Xu
    • 1
    Email author
  • Ling-yu Zhao
    • 2
    Email author
  • Peng-bo Yang
    • 3
  • Jian-shui Zhang
    • 3
  • Ying-fang Tian
    • 4
  1. 1.Department of Human AnatomyXi’an Medical UniversityXi’anPeople’s Republic of China
  2. 2.Department of Cell Biology and Genetics, School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’anPeople’s Republic of China
  3. 3.Department of Human Anatomy & Histo-embryology, School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’anPeople’s Republic of China
  4. 4.College of Life SciencesShaanxi Normal UniversityXi’anPeople’s Republic of China

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