Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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

Authors: Zhang, Qi-Shun  Liu, Wei  Lu, Guang-Xiu 
Citation: Zhang QS, etal., J Biosci. 2017 Sep;42(3):397-404.
Pubmed: (View Article at PubMed) PMID:29358553

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 (A β)-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 β 25-35. The results of flow cytometry analysis showed that the apoptosis rate and cleaved-caspase-3 expression in PC12 cells exposed to A β 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 β 25-35 + anti-miR-200a-3p group compared with the A β 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 β25-35-induced neuronal apoptosis and cleavedcaspase- 3 level in PC12 cells, whereas anti-miR-200a-3p reversed these effects. Knockdown of SIRT1 decreased the inhibitory effect of A β 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 β 25-35-induced apoptosis in PC12 cells by targeting SIRT1. Thus, miR-200a-3p may be a potential therapeutic target for treatment of AD.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 13838797
Created: 2019-01-16
Species: All species
Last Modified: 2019-01-16
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.