MiR-16-5p and miR-19b-3p prevent amyloid β-induced injury by targeting BACE1 in SH-SY5Y cells.

Abstract

Alzheimer's disease is the most common neurodegenerative disease, characterized by accumulation of amyloid β peptides. MicroRNAs have been identified as significant regulators and therapeutic targets of Alzheimer's disease. However, the roles of miR-16-5p and miR-19b-3p and their mechanisms in Alzheimer's disease progression remain largely unknown. Amyloid β-treated SH-SY5Y cells were used to study Alzheimer's disease progression in vitro. Transfection was conducted into SH-SY5Y cells using Lipofectamine 2000. The expression levels of miR-16-5p, miR-19b-3p and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) were measured by quantitative real-time PCR or western blot, respectively. Cell viability and apoptosis were detected in amyloid β-treated SH-SY5Y cells by MTT or flow cytometry, respectively. The interaction between BACE1 and miR-16-5p or miR-19b-3p was explored by luciferase reporter and RNA immunoprecipitation analyses. The expression levels of miR-16-5p and miR-19b-3p were reduced but BACE1 protein expression was enhanced in SH-SY5Y cells after treatment of amyloid β. Overexpression of miR-16-5p or miR-19b-3p attenuated amyloid β-induced viability inhibition and apoptosis promotion in SH-SY5Y cells, while their knockdown exacerbated amyloid β-induced injury. BACE1 was confirmed as a target of miR-16-5p and miR-19b-3p and its overexpression aggravated amyloid β-induced loss of viability and production of apoptosis, while its depletion caused an opposite effect. Moreover, upregulation of BACE1 alleviated the regulatory effects of miR-16-5p and miR-19b-3p on amyloid β-induced injury. MiR-16-5p and miR-19b-3p relieved amyloid β-induced injury by targeting BACE1 in SH-SY5Y cells, indicating miR-16-5p and miR-19b-3p as protective agents for treatment of Alzheimer's disease.