Reduced serum miR‐202 may promote the progression of Alzheimer's disease patients via targeting amyloid precursor protein

Abstract

Abstract The current study investigated whether the expression of miR‐202 was abnormal in the serum of patients with Alzheimer's disease (AD) and evaluated the potential clinical significance, thereby shedding light on the diagnosis of AD. Here, our data showed that the level of miR‐202 decreased significantly in the serum of AD patients (n = 121) compared with that of healthy controls (n = 86). Further analysis showed that the level of serum miR‐202 was gradually decreased in the mild AD group (n = 31), moderate AD group (n = 52) and severe AD group (n = 38) compared with the healthy control group. Receiver operating characteristic (ROC) curve analysis demonstrated that serum miR‐202 could differentiate AD patients from healthy controls, with an AUC of 0.892. Spearman correlation analysis showed that serum miR‐202 was positively correlated with the Mini‐Mental State Examination (MMSE). Based on TargetScan, a conserved binding site was identified in the 3′UTR of amyloid precursor protein (APP). The dual luciferase assay showed that miR‐202 suppressed the relative luciferase activity of pmirGLO‐APP‐3′UTR. Western blot assays indicated that overexpression of miR‐202 suppressed the expression of APP, while the expression of APP was enhanced after inhibition of miR‐202 in PC12 cells, indicating that APP was a possible target gene of miR‐202. Moreover, the cell apoptosis induced by transfection of miR‐202 inhibitor was abolished by silencing APP. In summary, we showed novel data that downregulation of serum miR‐202 may be used as a potential biomarker for AD and may promote the development of AD by targeting APP.

Keywords

• Alzheimer's disease
• amyloid precursor protein
• diagnosis
• miR‐202