Cited by 271MicroRNA in disease regulationAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer's disease, inhibits bcl2 translation

Wang, Xiaoying, Liu, Peng, Zhu, Hua, Xu, Yanfeng, Ma, Chunmei, Dai, Xiaowei, Huang, Lan, Liu, Yali +2 more·2009·Brain Research Bulletin

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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Crossref · 10.1016/j.brainresbull.2009.08.006

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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
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
  • Health Sciences › Medicine › Physiology › 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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