title: Downregulated miR-29c correlates with increased BACE1 expression in sporadic Alzheimer's disease.
abstract: BACKGROUND
  Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is conceived as a potential target for therapies against Alzheimer disease (AD) which is characterized by the accumulation of plaques formed of short β-amyloid (APPβ) peptides. Recently, such microRNAs, as miR-29a, miR-29b-1 have been shown to correlate with abnormally high levels of BACE1 and APPβ in sporadic AD.
  
  
  METHODS
  In order to confirm whether miR-29c correlates with the BACE1 upregulation in sporadic AD, we firstly evaluated the expression of miR-29c and BACE1, the APPβ accumulation in sporadic AD brain tissues and analyzed the correlation of miR-29c with BACE1. Then we determined the regulation of miR-29c in human heuroblastoma SH-SY5Y cells on the BACE1 expression and APPβ accumulation. And finally we determined the targeting to 3' UTR of BACE1 by miR-29c by a luciferase reporter.
  
  
  RESULTS
  It was demonstrated that miR-29c was downregulated in sporadic AD brains, in an association with an upregulation of BACE1 in both mRNA and protein level of BACE1, and also an elevated APPβ accumulation. And the manipulated high level of miR-29c with miR-29c mimics transfection significantly reduced the protein level of BACE1 and APPβ accumulation in human neuroblastoma SH-SY5Y cells. Further luciferase reporter assay demonstrated that miR-29c targets the 3' UTR of BACE1 and downregulated the BACE1 in HEK293 cells.
  
  
  CONCLUSIONS
  Present study indicated that miR-29c was downregulated in sporadic AD brains, and it targeted the 3' UTR of BACE1, reduced the BACE1 expression, and downregulated the APPβ accumulation in vitro.
authors.affiliation: Department of Neurology Medicine, Tianjin Medical University General Hospital Tanjin 300052, China ; Department of Neurology Medicine, Tianjin 4th Center Hospital Tianjin 300140, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lei
authors.affiliation: School of Public Health, Shanxi Medical University Taiyuan, Shanxi 030001, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Neurology Medicine, Tianjin Medical University General Hospital Tanjin 300052, China.
authors.forename: Zhelin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology Medicine, Tianjin 4th Center Hospital Tianjin 300140, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology Medicine, Tianjin Medical University General Hospital Tanjin 300052, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D015153:Blotting, Western; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: APPβ accumulation; Alzheimer’s disease; BACE1; miR-29c