Inhibition of miR-96-5p May Reduce Aβ42/Aβ40 Ratio via Regulating ATP-binding cassette transporter A1
| Autor: | Min Zhu, Jianping Jia, Longfei Jia |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell Line law.invention Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease law microRNA Animals Humans 3' Untranslated Regions Polymerase chain reaction Messenger RNA Amyloid beta-Peptides biology Three prime untranslated region Chemistry General Neuroscience Transporter General Medicine Peptide Fragments Cell biology Blot Disease Models Animal MicroRNAs Psychiatry and Mental health Clinical Psychology 030104 developmental biology ABCA1 biology.protein lipids (amino acids peptides and proteins) Geriatrics and Gerontology ATP-Binding Cassette Transporter A1 030217 neurology & neurosurgery ATP Binding Cassette Transporter 1 |
| Zdroj: | Journal of Alzheimer's Disease. 83:367-377 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background: Imbalance between amyloid-β (Aβ) production and clearance results in Aβ accumulation. Regulating Aβ levels is still a hot point in the research of Alzheimer’s disease (AD). Objective: To identify the differential expression of ATP-binding cassette transporter A1 (ABCA1) and its upstream microRNA (miRNA) in AD models, and to explore their relationships with Aβ levels. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the expression of ABCA1 in 5xFAD mice, SH-SY5Y cells treated with Aβ oligomers and SH-SY5YAβPP695 cells (AD models). TargetScan was used to predict the upstream miRNAs for ABCA1. Dual-luciferase assay was conducted to identify the regulation of the miRNA on ABCA1. qRT-PCR was used to measure the expression of miRNA in AD models. Finally, enzyme-linked immunosorbent assays were performed to detect Aβ42 and Aβ40 levels. Results: The expression of ABCA1 was significantly downregulated in AD models at both mRNA and protein levels. Dual-luciferase assay showed that miR-96-5p could regulate the expression of ABCA1 through binding to the 3 untranslated region of ABCA1. The level of miR-96-5p was significantly elevated in AD models. The expression of ABCA1 was enhanced while Aβ42 levels and Aβ42/Aβ40 ratios were reduced in SH-SY5YAβPP695 cells after treated with miR-96-5p inhibitor. Conclusion: The current study found that miR-96-5p is the upstream miRNA for ABCA1. Suppression of miR-96-5p in AD models could reduce Aβ42/Aβ40 ratios via upregulating the expression of ABCA1, indicating that miR-96-5p plays an important role in regulating the content of Aβ. |
| Databáze: | OpenAIRE |
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