title: Deregulation of miRNA-181c potentially contributes to the pathogenesis of AD by targeting collapsin response mediator protein 2 in mice.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is usually accompanied by abnormal gene expression. The 20 to 25 nucleotide (nt) tiny regulators, known as micro ribonucleic acids (miRNAs), have been found to play important roles in the etiology and pathogenesis of various biological processes. The purpose of the current study was to identify the aberrant expression of microRNAs in the hippocampus of an AD mouse model and to investigate its potential role during the progression of AD. The results from microarray analysis showed that several miRNAs were deregulated in the hippocampus tissue of SAMP8 mice compared to SAMR1 mice. Among the deregulated miRNAs, a significant decrease in miR-181c was validated by quantitative real-time PCR. Bioinformatic analysis revealed that miR-181c might be involved in the regulation of axon guidance, MAPK signaling, dorso-ventral axis formation and long-term depression. Moreover, the results of a luciferase activity assay, western blot analysis and immunofluorescent staining showed that over-expression of miR-181c targets the 3'-untranslated region (3'-UTR) of collapsin response mediator protein 2 (crmp2) through its binding sites and down-regulates crmp2 protein abundance at the post-transcriptional level. Taken together, these findings suggested that crmp2 is a target of miR-181c and that the abnormally low expression of miR-181c in the hippocampus of SAMP8 mice could lead to an increase of the crmp2 protein level in AD mice, which might potentially play a role in the pathogenesis of Alzheimer's disease.
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Lu
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yu
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xie
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cui
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Burn Engineering Center of Hebei Province, Shijiazhuang, PR China.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China. Electronic address: sjxu66@hotmail.com.
authors.forename: Shunjiang
authors.initials: S
authors.lastname: Xu
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; C529100:mirn181 microRNA, mouse
keywords: Alzheimer's disease (AD); Collapsin response mediator protein 2 (crmp2); Hippocampus; MicroRNA; SAM mice; miR-181c