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

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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.

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Abbreviations

OGD:

Oxygen-glucose deprivation

OGDR:

Oxygen-glucose deprivation/reperfusion

UTR:

Untranslated region

miR-25:

microRNA-25

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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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    Authors and Affiliations

    1. Department of Human Anatomy, Xi’an Medical University, No. 1, Xinwang Road, Weiyang District, Xi’an, 710021, People’s Republic of China

      Jun-feng Zhang, Li-li Shi, Li Zhang, Zhao-hua Zhao, Fei Liang & Xi Xu

    2. Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China

      Ling-yu Zhao

    3. Department of Human Anatomy & Histo-embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China

      Peng-bo Yang & Jian-shui Zhang

    4. College of Life Sciences, Shaanxi Normal University, Xi’an, 710062, People’s Republic of China

      Ying-fang Tian

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    1. Jun-feng Zhang
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    Correspondence to Xi Xu or Ling-yu Zhao.

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    Jun-feng Zhang and Li-li Shi contributed equally to this work.

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    Zhang, Jf., Shi, Ll., Zhang, L. et al. MicroRNA-25 Negatively Regulates Cerebral Ischemia/Reperfusion Injury-Induced Cell Apoptosis Through Fas/FasL Pathway. J Mol Neurosci 58, 507–516 (2016). https://doi.org/10.1007/s12031-016-0712-0

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