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miR-200a-3p promotes β-Amyloid-induced neuronal apoptosis through down-regulation of SIRT1 in Alzheimer’s disease

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Abstract

The aberrantly expressed microRNAs (miRNAs) including miR-200a-3p have been reported in the brains of Alzheimer’s disease (AD) patients in recent researches. Nevertheless, the role of miR-200a-3p in AD has not been characterized. The purpose of this study was to examine whether miR-200a-3p regulated β-Ameyloid (Aβ)-induced neuronal apoptosis by targeting SIRT1, a known anti-apoptotic protein. An increased level of miR-200a-3p and a decreased level of SIRT1 in the hippocampus of APPswe/PSΔE9 mice (a model for AD) were observed. To construct an in vitro cell model of AD, PC12 cells were cultured in presence of Aβ25-35. The results of flow cytometry analysis showed that the apoptosis rate and cleaved-caspase-3 expression in PC12 cells exposed to Aβ25-35 were remarkably increased, but the apoptosis rate and cleaved-caspase-3 activity were decreased when cells were transfected with anti-miR-200a-3p. On the other hand, MTT assay showed that the cell survival rate was increased in the Aβ25-35 + anti-miR-200a-3p group compared with the Aβ25-35 + anti-miR-NC group. Dual-luciferase reporter gene assay validated the predicted miR-200a-3p binding sites in the 3′-UTR of SIRT1 mRNA. In addition, downregulation of SIRT1 promoted Aβ25-35-induced neuronal apoptosis and cleaved-caspase-3 level in PC12 cells, whereas anti-miR-200a-3p reversed these effects. Knockdown of SIRT1 decreased the inhibitory effect of Aβ25-35 on cell viability, while anti-miR-200a-3p attenuated this effect. Overall, the results suggest that suppression of miR-200a-3p attenuates Aβ25-35-induced apoptosis in PC12 cells by targeting SIRT1. Thus, miR-200a-3p may be a potential therapeutic target for treatment of AD.

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Acknowledgements

This work is supported by the Natural Science Foundation of China (81401062, 81601123), and Grant from the Education Department of Henan Province (15A310003).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Huaihe Hospital of Henan University, Kaifeng, 475000, China

    Qi-Shun Zhang, Wei Liu & Guang-Xiu Lu

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  1. Qi-Shun Zhang
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  2. Wei Liu
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  3. Guang-Xiu Lu
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Correspondence to Guang-Xiu Lu.

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Corresponding editor: Ullas Kolthur

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Zhang, QS., Liu, W. & Lu, GX. miR-200a-3p promotes β-Amyloid-induced neuronal apoptosis through down-regulation of SIRT1 in Alzheimer’s disease. J Biosci 42, 397–404 (2017). https://doi.org/10.1007/s12038-017-9698-1

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  • DOI: https://doi.org/10.1007/s12038-017-9698-1

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