title: Regulatory factor X1 depresses ApoE-dependent Aβ uptake by miRNA-124 in microglial response to oxidative stress.
abstract: Decreased proteolytic clearance of soluble amyloid β (Aβ) in microglia affects Aβ accumulation on Alzheimer's disease progression. However, the potential molecular mechanism by which microglial Aβ uptake is regulated remains unclear. In this study, we identified a microRNA, miR-124, that was down-regulated in aging with a function in regulating apolipoprotein E (ApoE)-dependent Aβ uptake by targeting regulatory factor X1 (RFX1) transcripts on BV2 microglia cell. Decreased expression of miRNA-124 in BV2 cells exposed to mild hydrogen peroxide increased RFX1 protein level and decreased the expression of ApoE, a gene which has been suggested to enhance cellular Aβ uptake in microglia. We also identified a miR-124 binding site in the 3'-UTR of RFX1 mRNA and a RFX1 binding site in the first intron of ApoE gene. Furthermore, interfering this signaling pathway by knocking down RFX1 significantly improved Aβ uptake in BV2 cells. These data demonstrate the mechanism through which decreased miR-124 expression under oxidative stress slowed Aβ uptake and suggest that RFX1 might be a target for improving Aβ clearance during aging.
authors.affiliation: Department of Basic Medical Sciences, Hangzhou Medical College, Hangzhou 310053, Zhejiang, China; Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. Electronic address: fengchenzhuo@hotmail.com.
authors.forename: Chen-Zhuo
authors.initials: CZ
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Yin
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China. Electronic address: caolin@mail.sysu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001665:Binding Sites; D002470:Cell Survival / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D000071716:Regulatory Factor X1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; C000605537:RFX1 protein, human; D012333:RNA, Messenger; D000071716:Regulatory Factor X1; C000605538:Rfx1 protein, mouse; D006861:Hydrogen Peroxide
keywords: Alzheimer’s disease; ApoE; Aβ uptake; RFX1; miR-124