title: MicroRNA-138 promotes tau phosphorylation by targeting retinoic acid receptor alpha.
abstract: 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.
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xiong
authors: X
authors: Wang
authors: Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China.
authors: Lu
authors: L
authors: Tan
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yanjun
authors: Y
authors: Lu
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Jing
authors: J
authors: Peng
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yaowu
authors: Y
authors: Zhu
authors: Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China. Electronic address: yadong-zhang@hotmail.com.
authors: Yadong
authors: Y
authors: Zhang
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: tjszyong@163.com.
authors: Ziyong
authors: Z
authors: Sun
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D016875:tau Proteins
keywords: Alzheimer’s disease; Glycogen synthase kinase-3β; Phosphorylation; Retinoic acid receptor alpha; Tau; miR-138