B Zhang1, C-F Chen, A-H Wang, Q-F Lin. 1. Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China. chencf301@163.com.
Abstract
OBJECTIVE: The aim of this study was to investigate the role of miR-16 in Alzheimer's disease (AD) and to explore its mechanism of action. MATERIALS AND METHODS: A cellular AD model using PC12 cells and primary hippocampal neurons was established to evaluate the expression level of miR-16. Transfection of a miR-16 mimic and a miR-16 inhibitor were performed to explore its effect on cell apoptosis and cell viability. In addition, we carried out bioinformatics analysis, luciferase reporting gene assay, and gene expression analyses to identify the potential target of miR-16 and to verify the effect of the target gene on the cellular AD model. RESULTS: Downregulation of miR-16 was confirmed in the cellular AD model with both PC12 cells (p < 0.05) and primary hippocampal neurons (p < 0.05). Overexpression and inhibition of miR-16 in the cellular AD model with primary hippocampal neurons decreased and increased apoptosis, respectively. The gene encoding amyloid precursor protein (APP) was identified as the target gene of miR-16. Knockdown of APP in primary hippocampal neurons decreased cell apoptosis and increased cell viability in the cellular AD model. CONCLUSIONS: Our results demonstrate that downregulation of miR-16 in primary hippocampal neurons play an important role in the paracrine effect and might be involved in the development of AD.
OBJECTIVE: The aim of this study was to investigate the role of miR-16 in Alzheimer's disease (AD) and to explore its mechanism of action. MATERIALS AND METHODS: A cellular AD model using PC12 cells and primary hippocampal neurons was established to evaluate the expression level of miR-16. Transfection of a miR-16 mimic and a miR-16 inhibitor were performed to explore its effect on cell apoptosis and cell viability. In addition, we carried out bioinformatics analysis, luciferase reporting gene assay, and gene expression analyses to identify the potential target of miR-16 and to verify the effect of the target gene on the cellular AD model. RESULTS: Downregulation of miR-16 was confirmed in the cellular AD model with both PC12 cells (p < 0.05) and primary hippocampal neurons (p < 0.05). Overexpression and inhibition of miR-16 in the cellular AD model with primary hippocampal neurons decreased and increased apoptosis, respectively. The gene encoding amyloid precursor protein (APP) was identified as the target gene of miR-16. Knockdown of APP in primary hippocampal neurons decreased cell apoptosis and increased cell viability in the cellular AD model. CONCLUSIONS: Our results demonstrate that downregulation of miR-16 in primary hippocampal neurons play an important role in the paracrine effect and might be involved in the development of AD.
Authors: Paul M McKeever; Raphael Schneider; Foad Taghdiri; Anna Weichert; Namita Multani; Robert A Brown; Adam L Boxer; Anna Karydas; Bruce Miller; Janice Robertson; Maria Carmela Tartaglia Journal: Mol Neurobiol Date: 2018-03-30 Impact factor: 5.590