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

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    • Keywords


      Alzheimer’s; apoptosis; miR-200a-3p; SIRT1; β-amyloid

    • Abstract


      The aberrantly expressed microRNAs (miRNAs) including miR-200a-3p have been reported in the brains of Alzheimer’sdisease (AD) patients in recent researches. Nevertheless, the role of miR-200a-3p in AD has not been characterized. Thepurpose of this study was to examine whether miR-200a-3p regulated b-Ameyloid (Ab)-induced neuronal apoptosis bytargeting SIRT1, a known anti-apoptotic protein. An increased level of miR-200a-3p and a decreased level of SIRT1 in thehippocampus of APPswe/PSDE9 mice (a model for AD) were observed. To construct an in vitro cell model of AD, PC12cells were cultured in presence of Ab25-35. The results of flow cytometry analysis showed that the apoptosis rate andcleaved-caspase-3 expression in PC12 cells exposed to Ab25-35 were remarkably increased, but the apoptosis rate andcleaved-caspase-3 activity were decreased when cells were transfected with anti-miR-200a-3p. On the other hand, MTTassay showed that the cell survival rate was increased in the Ab25-35 ? anti-miR-200a-3p group compared with the Ab25-35 ? anti-miR-NC group. Dual-luciferase reporter gene assay validated the predicted miR-200a-3p binding sites in the 30-UTR of SIRT1 mRNA. In addition, downregulation of SIRT1 promoted Ab25-35-induced neuronal apoptosis and cleavedcaspase-3 level in PC12 cells, whereas anti-miR-200a-3p reversed these effects. Knockdown of SIRT1 decreased theinhibitory effect of Ab25-35 on cell viability, while anti-miR-200a-3p attenuated this effect. Overall, the results suggest thatsuppression of miR-200a-3p attenuates Ab25-35-induced apoptosis in PC12 cells by targeting SIRT1. Thus, miR-200a-3pmay be a potential therapeutic target for treatment of AD.

    • Author Affiliations



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

  • Journal of Biosciences | News

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