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. 2013 Jun 5;29(6):745–751. doi: 10.1007/s12264-013-1348-5

MicroRNA-98 induces an Alzheimer’s disease-like disturbance by targeting insulin-like growth factor 1

Yi-Kui Hu 1, Xun Wang 2, Lian Li 3, Yan-Hua Du 3, Heng-Tai Ye 3, Cheng-Yan Li 4,✉
PMCID: PMC5561832  PMID: 23740209

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Many microRNAs (miRs) participate in regulating amyloid β (Aβ) formation and the metabolism of tau protein in the process of AD, and some are up-regulated in AD patients or transgenic models of AD. However, the role of miR-98 in AD remains unclear. Here, we showed that the expression of miR-98 was negatively correlated with the insulin-like growth factor 1 (IGF-1) protein level in APP/PS1 mice. MiR-98 target sites in IGF-1 were confirmed by luciferase assay in HEK293 cells. Overexpression of miR-98 in N2a/APP cells down-regulated the IGF-1 protein level and promoted Aβ production, whereas inhibition of miR-98 in N2a/APP cells up-regulated the IGF-1 protein level and suppressed Aβ production. Furthermore, overexpression of miR-98 in N2a/WT cells increased the phosphorylation of tau, whereas inhibition of miR-98 reduced it. These results suggest that miR-98 increases Aβ formation and tau phosphorylation by inhibiting the translation of IGF-1, which might provide a therapeutic strategy for AD.

Keywords: Alzheimer’s disease, microRNA, miR-98, IGF-1

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