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

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 beta-Ameyloid (A beta)-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/PS Delta E9 mice (a model for AD) were observed. To construct an in vitro cell model of AD, PC12 cells were cultured in presence of A beta(25-35). The results of flow cytometry analysis showed that the apoptosis rate and cleaved-caspase-3 expression in PC12 cells exposed to A beta(25-35) 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 A beta(25-35) + anti-miR-200a-3p group compared with the A beta(25-35) + 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 A beta(25-35)-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 A beta(25-35) on cell viability, while anti-miR-200a-3p attenuated this effect. Overall, the results suggest that suppression of miR-200a-3p attenuates A beta(25-35)-induced apoptosis in PC12 cells by targeting SIRT1. Thus, miR-200a-3p may be a potential therapeutic target for treatment of AD.