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

Abstract

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, miR-222 was observed to be downregulated in APPswe/PSΔE9 mice (a model for AD) compared with age-matched controls. Furthermore, the downregulation of miR-222 was correlated with increased p27Kip1 protein levels. Bioinformatic analysis showed that there was one highly-conserved putative binding site for miR-222 in the 3'-UTR of p27Kip1. Luciferase reporter assays confirmed that p27Kip1 was a direct target of miR-222. Consistently, there was an inverse correlation between p27Kip1 and miR-222 expression levels in SH-SY5Y cells. In conclusion, these results suggest that the abnormal expression of miR-222 may contribute to dysregulation of the cell-cycle in AD, at least in part by affecting the expression of p27Kip1.