The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression through Regulation of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1
By Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson. Journal of Neuroscience, 2008
840 citations recorded by the source corpus.
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 β-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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/433a1c107fd282205dca95be0e2a3843900cb1e5
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Citations in the corpus
- miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis (2020, background): “In the cortex of AD patients, regardless of stage, miR-107 is poorly expressed [258].”
- miR-155 gene: a typical multifunctional microRNA. (2009, background): “The 3'UTR of BACE1 mRNA can be targeted in multiple sites by miR-107 suggesting that miR-107 is one of the multifactorial causes involved in AD progression [21].”
- MicroRNAs in development and disease. (2011, background): “Similarly, miR-107 is downregulated during early stages of AD and also directly targets BACE1 (653).”
- microRNA as Biomarkers and Diagnostics (2016, background): “For example, low miR-107 expression is found in the cortex of Alzheimer’s disease patients, even at extremely early-stage pathological alterations (Wang et al., 2008), and the expression levels of miR-1, miR-22 , and miR-29 may be useful for distinguishing between those with nontreated Parkinson’s…”
- Non-coding RNAs in human disease (2011, background): “For example, in Alzheimer's disease, abnormally expressed miRNAs have consistently been reported as downregulating the expression of the enzyme β-secretase 1 (BACE1), which leads to the production of β-amyloid peptid”