title: Screening of microRNAs associated with Alzheimer's disease using oxidative stress cell model and different strains of senescence accelerated mice.
abstract: Oxidative stress plays a critical role in the etiology and pathogenesis of Alzheimer's disease (AD), and the molecular mechanisms that control the neuron response to oxidative stress have been extensively studied. However, the effects of oxidative stress on miRNA expression in hippocampal neurons has not been investigated, and little is known about the roles of ROS-modulated miRNAs in cell function as yet. In this study, miRNA microarray technology was used to analyze the expression of miRNAs in the oxidative stressed primary hippocampal neurons, hippocampus of senescence accelerated mouse prone 8 (SAMP8) and prone 10 (SAMP10). The targets of co-regulated microRNAs were also selected for computational prediction using miRWalk software and functional analysis by the DAVID software. In addition, the changes of co-regulated microRNA expression were validated by quantitative real-time PCR. The results of microarray analysis showed that miR-329, miR-193b, miR-20a, miR-296, and miR-130b were all upregulated in H2O2-induced primary hippocampal neurons and different strains of senescence accelerated mice. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these co-regulated microRNAs may be involved in the regulation of cell growth, apoptosis, signal transmission and cancer development. In which, mitogen-activated protein kinase (MAPK) signaling pathway was one of the most significant pathways to be affected by 83 target genes of miR-329, miR-193b, miR-20a miR-296, and miR-130b. The quantitative real-time PCR data confirmed the alterations of the co-upregulated miRNAs. These results suggested that oxidative stress alters the miRNA expression profile of hippocampal neurons, and the deregulated miRNAs might play potential roles in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). This study provided a strong basis for the future study aiming at contributions of miRNAs induced by oxidative stress in AD.
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Burns and Plastic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Hebei Provincial Geriatric Hospital, Shijiazhuang, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Niu
authors.affiliation: Department of Clinical Laboratory, Hebei Provincial Geriatric Hospital, Shijiazhuang, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Lu
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xie
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cui
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: sjxu66@hotmail.com.
authors.forename: Shunjiang
authors.initials: S
authors.lastname: Xu
mesh_terms: D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D035683:MicroRNAs; D006861:Hydrogen Peroxide
keywords: Alzheimer disease; Array analysis; Hippocampal neurons; Oxidative stress; Senescence-accelerated mouse; microRNA