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Publication : Downregulated microRNA-222 is correlated with increased p27Kip¹ expression in a double transgenic mouse model of Alzheimer's disease.

First Author  Wang X Year  2015
Journal  Mol Med Rep Volume  12
Issue  5 Pages  7687-92
PubMed ID  26398571 Mgi Jnum  J:347007
Mgi Id  MGI:6884161 Doi  10.3892/mmr.2015.4339
Citation  Wang X, et al. (2015) Downregulated microRNA-222 is correlated with increased p27Kip(1) expression in a double transgenic mouse model of Alzheimer's disease. Mol Med Rep 12(5):7687-92
abstractText  MicroRNAs (miRNAs) are a group of endogenous non-coding small RNAs that regulate protein expression by binding to the 3' untranslated region (UTR) of target genes. miRNAs are abundantly expressed in the central nervous system and participate in neuronal differentiation and synaptic plasticity. However, the possible roles and associated target genes of miRNAs in Alzheimer's disease (AD) are largely unknown. In the current study, miR222 was observed to be downregulated in APPswe/PSDeltaE9 mice (a model for AD) compared with agematched controls. Furthermore, the downregulation of miR222 was correlated with increased p27Kip1 protein levels. Bioinformatic analysis showed that there was one highlyconserved putative binding site for miR222 in the 3'UTR of p27Kip1. Luciferase reporter assays confirmed that p27Kip1 was a direct target of miR222. Consistently, there was an inverse correlation between p27Kip1 and miR222 expression levels in SHSY5Y cells. In conclusion, these results suggest that the abnormal expression of miR222 may contribute to dysregulation of the cellcycle in AD, at least in part by affecting the expression of p27Kip1.
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