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The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1.
J Neurosci. 2008 Jan 30; 28(5):1213-23.JN

Abstract

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with the earliest stages of pathology. In situ hybridization with cross-comparison to neuropathology demonstrated that particular cerebral cortical laminas involved by AD pathology exhibit diminished neuronal miR-107 expression. Computational analysis predicted that the 3'-untranslated region (UTR) of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA is targeted multiply by miR-107. From the same RNA material analyzed on miRNA microarrays, mRNA expression profiling was performed using Affymetrix Exon Array microarrays on nondemented, MCI, and AD patients. BACE1 mRNA levels tended to increase as miR-107 levels decreased in the progression of AD. Cell culture reporter assays performed with a subset of the predicted miR-107 binding sites indicate the presence of at least one physiological miR-107 miRNA recognition sequence in the 3'-UTR of BACE1 mRNA. Together, the coordinated application of miRNA profiling, Affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that miR-107 may be involved in accelerated disease progression through regulation of BACE1.

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Authors+Show Affiliations

Wang WX
Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536, USA.
Rajeev BW
No affiliation info available
Stromberg AJ
No affiliation info available
Ren N
No affiliation info available
Tang G
No affiliation info available
Huang Q
No affiliation info available
Rigoutsos I
No affiliation info available
Nelson PT
No affiliation info available

MeSH

AgedAged, 80 and overAlzheimer DiseaseAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesDisease ProgressionFemaleGene Expression RegulationHumansMaleMicroRNAsTime Factors

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18234899

Citation

Wang, Wang-Xia, et al. "The Expression of microRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression Through Regulation of Beta-site Amyloid Precursor Protein-cleaving Enzyme 1." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 5, 2008, pp. 1213-23.
Wang WX, Rajeev BW, Stromberg AJ, et al. The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci. 2008;28(5):1213-23.
Wang, W. X., Rajeev, B. W., Stromberg, A. J., Ren, N., Tang, G., Huang, Q., Rigoutsos, I., & Nelson, P. T. (2008). The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(5), 1213-23. https://doi.org/10.1523/JNEUROSCI.5065-07.2008
Wang WX, et al. The Expression of microRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression Through Regulation of Beta-site Amyloid Precursor Protein-cleaving Enzyme 1. J Neurosci. 2008 Jan 30;28(5):1213-23. PubMed PMID: 18234899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. AU - Wang,Wang-Xia, AU - Rajeev,Bernard W, AU - Stromberg,Arnold J, AU - Ren,Na, AU - Tang,Guiliang, AU - Huang,Qingwei, AU - Rigoutsos,Isidore, AU - Nelson,Peter T, PY - 2008/2/1/pubmed PY - 2008/2/20/medline PY - 2008/2/1/entrez SP - 1213 EP - 23 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 28 IS - 5 N2 - MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with the earliest stages of pathology. In situ hybridization with cross-comparison to neuropathology demonstrated that particular cerebral cortical laminas involved by AD pathology exhibit diminished neuronal miR-107 expression. Computational analysis predicted that the 3'-untranslated region (UTR) of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA is targeted multiply by miR-107. From the same RNA material analyzed on miRNA microarrays, mRNA expression profiling was performed using Affymetrix Exon Array microarrays on nondemented, MCI, and AD patients. BACE1 mRNA levels tended to increase as miR-107 levels decreased in the progression of AD. Cell culture reporter assays performed with a subset of the predicted miR-107 binding sites indicate the presence of at least one physiological miR-107 miRNA recognition sequence in the 3'-UTR of BACE1 mRNA. Together, the coordinated application of miRNA profiling, Affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that miR-107 may be involved in accelerated disease progression through regulation of BACE1. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/18234899/The_expression_of_microRNA_miR_107_decreases_early_in_Alzheimer's_disease_and_may_accelerate_disease_progression_through_regulation_of_beta_site_amyloid_precursor_protein_cleaving_enzyme_1_ DB - PRIME DP - Unbound Medicine ER -