MiR-124-3p attenuates hyperphosphorylation of tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells

// Qingmei Kang 1, 2, * , Yue Xiang 1, 2, * , Dan Li 1, 2 , Jie Liang 1, 2 , Xiong Zhang 2 , Fanlin Zhou 1, 2 , Mengyuan Qiao 1, 2 , Yingling Nie 1, 2 , Yurong He 1, 2 , Jingyi Cheng 1, 2 , Yubing Dai 3 , Yu Li 1, 2 1 Department of Pathology, Chongqing Medical University, Chongqing, 400016, China 2 Center for Molecular Medicine Testing, Chongqing Medical University, Chongqing, 400016, China 3 Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China * These authors contributed equally to this work Correspondence to: Yu Li, email: [email protected] Keywords: miR-124-3p, tau, caveolin-1, PI3K/Akt/GSK3β, Alzheimer's disease Received: November 02, 2016      Accepted: January 24, 2017      Published: February 07, 2017 ABSTRACT Hyperphosphorylation of Tau forming neurofibrillary tangles has been considered as a crucial event in the pathogenesis of Alzheimer's disease (AD). MiR-124-3p belongs to microRNA (miRNA) family and was markedly decreased in AD, however, the functions of miR-124-3p in the pathogenesis of AD remain unknown. We observed that the expression of miR-124-3p was significantly decreased in N2a/APP695swe cells; and transfection of miR-124-3p mimics not only attenuated cell apoptosis and abnormal hyperphosphorylation of Tau protein without any changes of total Tau protein, but also increased expression levels of Caveolin-1, phosphoinositide 3-kinase (PI3K), phospho-Akt (Akt-Ser473)/Akt, phospho-glycogen synthase kinase-3 beta (GSK-3β-Ser9)/GSK-3β in N2a/APP695swe cells. We further found that miR-12-3p directly targeted Caveolin-1; miR-124-3p inhibited abnormal hyperphosphorylation of Tau by regulating Caveolin-1-PI3K/Akt/GSK3β pathway in AD. This study reveals that miR-124-3p may play a neuroprotective role in AD, which may provide new ideas and therapeutic targets for AD.

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