MicroRNA-138 promotes tau phosphorylation by targeting retinoic acid receptor alpha.
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.
['Wang|Xiong|X|', 'Tan|Lu|L|', 'Lu|Yanjun|Y|', 'Peng|Jing|J|', 'Zhu|Yaowu|Y|', 'Zhang|Yadong|Y|', 'Sun|Ziyong|Z|']
D000544:Alzheimer Disease D001483:Base Sequence D001665:Binding Sites D015870:Gene Expression D057809:HEK293 Cells D006801:Humans D035683:MicroRNAs D010766:Phosphorylation D011499:Protein Processing, Post-Translational D034622:RNA Interference D018168:Receptors, Retinoic Acid D000072482:Retinoic Acid Receptor alpha D016875:tau Proteins
Tau Phosphorylation Retinoic acid receptor alpha miR-138 Glycogen synthase kinase-3β Alzheimer’s disease