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

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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, Zhang, Lianfeng, Qin, Chuan·2009·Brain Research Bulletin

DOI 10.1016/j.brainresbull.2009.08.006

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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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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: Wang, Xiaoying
Liu, Peng
Zhu, Hua
Xu, Yanfeng
Dai, Xiaowei
Huang, Lan
Liu, Yali
Zhang, Lianfeng
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)
DOI: 10.1016/j.brainresbull.2009.08.006
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer's disease, inhibits bcl2 translation

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