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.

• Authors: Xiaoying Wang, Peng Liu, Hua Zhu, Yanfeng Xu, Chunmei Ma, Xiaowei Dai, Lan Huang, Yali Liu, Lianfeng Zhang, Chuan Qin
• Journal: Brain research bulletin (Brain Res Bull) Vol. 80 Issue 4-5 Pg. 268-73 (Oct 28 2009) ISSN: 1873-2747 [Electronic] United States
• PMID: 19683563 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• MicroRNAs
• Presenilin-1
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Bcl2 protein, mouse
• Caspase 3

Topics

• Alzheimer Disease (genetics, metabolism)
• Amyloid beta-Peptides (genetics)
• Animals
• Apoptosis
• Blotting, Western
• Caspase 3 (metabolism)
• Cells, Cultured
• Mice
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Microarray Analysis
• Presenilin-1 (genetics)
• Protein Biosynthesis (genetics)
• Proto-Oncogene Proteins (biosynthesis)
• Proto-Oncogene Proteins c-bcl-2
• Reverse Transcriptase Polymerase Chain Reaction