Inhibition of miR-96-5p May Reduce Aβ42/Aβ40 Ratio via Regulating ATP-binding cassette transporter A1

Background: Imbalance between amyloid-beta (A beta) production and clearance results in A beta accumulation. Regulating A beta 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 A beta 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 A beta oligomers and SH-SY5YA(beta PP695) 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 A beta(42) and A beta(40) levels. Results: The expression of ABCA1 was significantly downregulated in AD models at both mRNA and protein levels. Dualluciferase 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 A beta(42) levels and A beta(42)/A beta(40) ratios were reduced in SH-SY5YA(beta PP695) 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 A beta(42)/A beta(40) ratios via upregulating the expression of ABCA1, indicating that miR-96-5p plays an important role in regulating the content of A beta.