title: MicroRNA-98 induces an Alzheimer's disease-like disturbance by targeting insulin-like growth factor 1.
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.
authors.affiliation: Medical School of Wuhan University, Wuhan, 430060, China.
authors.forename: Yi-Kui
authors.initials: YK
authors.lastname: Hu
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Du
authors.forename: Heng-Tai
authors.initials: HT
authors.lastname: Ye
authors.forename: Cheng-Yan
authors.initials: CY
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C557404:MIRN98 microRNA, mouse; D035683:MicroRNAs; C519530:insulin-like growth factor-1, mouse; D016875:tau Proteins; D007334:Insulin-Like Growth Factor I