The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer's disease, inhibits bcl2 translation
Abstract
MicroRNAs (miRNAs) are short noncoding regulatory RNA molecules that modulate protein expression by inhibiting mRNA translation or promoting mRNA degradation. However, little is understood about the roles of miRNAs in Alzheimer's disease. During a research for miRNAs that are differentially expressed in cerebral cortex of APPswe/PSDeltaE9 mice (a model for Alzheimer's disease) and age-matched controls, one candidate miRNA that is relatively highly expressed, miR-34a, was studied further because sequence analysis suggested a likely interaction with the 3'-untranslated region of bcl2 mRNA. We show that the expression of miR-34a is inversely correlated with the protein level of bcl2 in APPswe/PSDeltaE9 mice and age-matched controls, and miR-34a expression directly inhibits bcl2 translation in SH-SY5Y cells. No effect on bcl2 mRNA level was observed. Western blot analysis of active caspase-3 showed higher levels in APPswe/PSDeltaE9 mice and stable transfecant cell line of miR-34a than in controls. Consistently, miR-34a knockdown through antisense LNA oligonucleotides increased the level of bcl2 protein in SH-SY5Y cells, which was accompanied by a decrease of active caspase-3. These findings suggested that bcl2 is an important functional target for miR-34a, and the abnormal expression of miR-34a may contribute to the pathogenesis of Alzheimer's disease, at least in part by affecting the expression of bcl2.
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“Interestingly, miR-106b levels were significantly decreased in brains of AD cases and AD mouse model (Hebert et al., 2009; Wang et al., 2011; Wang et al., 2009).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Wang et al., 2009
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Metadata
- Authors
- Wang, X., Liu, P., Zhu, H., Xu, Y., Ma, C., Dai, X., Huang, L., Liu, Y., Zhang, L., & Qin, C.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Qin, Chuan
- ORCID
- Venue
- Brain Research Bulletin
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 80
- Issue
- 4-5
- Pages
- 268-273
- ISSN
- 0361-9230 (ISSN-L)
- OpenAlex
- W1968383275
- Cited by
- 271
- References
- 29
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 23 · 2019: 16 · 2018: 18 · 2017: 20 · 2016: 15 · 2015: 24 · 2014: 23 · 2013: 21 · 2012: 17
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- miR-34a, microRNA, Alzheimer's disease, Bcl-2, protein synthesis inhibition, 3' untranslated region, caspase-3, neuronal apoptosis, SH-SY5Y cells, cerebral cortex
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Mice, Transgenic, Proto-Oncogene Proteins, Protein Biosynthesis, Blotting, Western, Amyloid beta-Peptides, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Microarray Analysis, Mice, Caspase 3, Presenilin-1
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