MiR-16 attenuates β-amyloid-induced neurotoxicity through targeting β-site amyloid precursor protein-cleaving enzyme 1 in an Alzheimer’s disease cell model

Abstract

The aberrant deposition of β-amyloid (Aβ) is closely linked to the pathogenesis and development of Alzheimer's disease (AD). MiR-16 was abnormally downregulated and may be related to the development of AD. However, the functional role and molecular mechanism of miR-16 in AD pathogenesis are still not well elucidated. The expressions of miR-16 and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein levels in AD brain tissues and Aβ-treated PC12 cellular AD model were examined by qRT-PCR and western blot analyses. Luciferase reporter assay was used to verify the potential target of miR-16. The cell viability, apoptosis, and caspase-3 activity in PC12 cells were determined by the MTT assay, flow cytometry analysis, and caspase-3 activity assay, respectively. Downregulation of miR-16 and upregulation of BACE1 existed in AD tissues and the cellular AD model of PC12. In addition, miR-16 directly suppressed BACE1 expression. Moreover, miR-16 overexpression and BACE1 knockdown facilitated Aβ-induced cell toxicity, apoptosis, and caspase-3 activity in N2a cells, which was partially eliminated by overexpression of BACE1. In contrast, BACE1 knockdown reversed the miR-16 inhibition-mediated inhibitory effect on Aβ-induced cell toxicity, apoptosis, and caspase-3 activity in PC12 cells. Collectively, miR-16 attenuated Aβ-induced neurotoxicity through targeting BACE1 in an Aβ insult cellular AD model, providing a potential therapeutic target for AD treatment.

The Role of Non-coding RNAs in Alzheimer’s Disease: From Regulated Mechanism to Therapeutic Targets and Diagnostic Biomarkers

“…The expression of crucial miRNAs that are potentially involved in regulating the expression of BACE1 appears to be decreased in the brains of patients with AD. For instance, the expression of miR-107, miR-29a/b-1, miR-29c, miR-188-3p, miR-339-5p, miR-195, miR-186, and miR-16 is decreased in the brains of patients with AD and AD mice (Hebert et al, 2008;Zhu et al, 2012;Long et al, 2014;Zhang J. et al, 2014;Lei et al, 2015;Jiao et al, 2016;Kim et al, 2016;Zhong et al, 2018). Studies have confirmed that these miRNAs regulate BACE1 expression levels by targeting the 3 -UTR region of the BACE1 mRNA.…”

Role of miR‐211 in a PC12 cell model of Alzheimer's disease via regulation of neurogenin 2

“…PC12 cells induced by Aβ 1–42 was established as a ell model (Zhong et al., 2018). Aβ 1–42 (Sigma‐Aldrich) was dissolved in double distilled water to prepare a 0.5 mM storage solution and then frozen at −20℃.…”

Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

“…miR-338-5p also regulates BACE-1 expression by targeting its mRNA, and expression of this micro-RNA leads to increased Aβ formation in brain tissues [122]. Downregulated miR-29a/29b1/c, miR-338-5p and miR-16 are all linked to increased Aβ-mediated neurotoxicity in vitro and in vivo [113]. Among those microRNAs, miR-338-5p also regulates NF-kB signaling and promotes neuroinflammation [122].…”