Clinical significance of miR-433 in the diagnosis of Alzheimer's disease and its effect on Aβ-induced neurotoxicity by regulating JAK2.

Abstract

Numerous microRNAs (miRNAs) have been investigated in the progression of Alzheimer's disease (AD). The purpose of this study was to analyze the expression of miR-433 and its diagnostic value in patients with AD, and to explore the neuroprotective effect of miR-433 in amyloid β (Aβ)-treated SH-SY5Y and SK-N-SH cells. AD patients and AD cell model that established by Aβ treatment were used in this study. Quantitative real-time PCR was used to measure the expression of miR-433. The diagnostic value of miR-433 was evaluated using the receiver operating characteristic analysis. MTT assay was used to examine the viability of Aβ-treated SH-SY5Y and SK-N-SH cells. Bioinformatics and luciferase activity analyses were used to confirm the target gene that might be involved in the mechanisms of miR-433 in AD. Expression levels of miR-433 were decreased in AD patients and cells compared with the corresponding controls. The decreased miR-433 expression levels in serum and cerebrospinal fluid (CS) were positively correlated with MMSE scores and had relatively high diagnostic accuracy in AD patients. The gain-of-function experiments found that the overexpression of miR-433 could rescue the Aβ-induced inhibition in neuronal viability in SH-SY5Y and SK-N-SH cells. The luciferase activity results showed that JAK2 was a target gene of miR-433 in neuronal cells. All the data of this study showed that miR-433 serves as a candidate diagnostic biomarker for AD patients, and may have the potential as a novel therapeutic target by ameliorating Aβ-induced neurotoxicity.