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.
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