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MicroRNA‐138 promotes tau phosphorylation by targeting retinoic acid receptor alpha
Author(s) -
Wang Xiong,
Tan Lu,
Lu Yanjun,
Peng Jing,
Zhu Yaowu,
Zhang Yadong,
Sun Ziyong
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.02.001
Subject(s) - phosphorylation , gsk 3 , microrna , retinoic acid , hek 293 cells , tau protein , chemistry , microbiology and biotechnology , gsk3b , glycogen synthase , cancer research , biology , receptor , alzheimer's disease , biochemistry , medicine , gene , disease
Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by Aβ deposition and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Emerging evidence shows that microRNAs (miRNAs) contribute to the pathogenesis of AD. Herein, we investigated the role of miR‐138, a brain enriched miRNA, which is increased in AD patients. We found that miR‐138 is increased in AD models, including N2a/APP and HEK293/tau cell lines. Overexpression of miR‐138 activates glycogen synthase kinase‐3β (GSK‐3β), and increases tau phosphorylation in HEK293/tau cells. Furthermore, we confirm that retinoic acid receptor alpha (RARA) is a direct target of miR‐138, and supplement of RARA substantially suppresses GSK‐3β activity, and reduces tau phosphorylation induced by miR‐138. In conclusion, our data suggest that miR‐138 promotes tau phosphorylation by targeting the RARA/GSK‐3β pathway.