Long non-coding RNA ANRIL knockdown suppresses apoptosis and pro-inflammatory cytokines while enhancing neurite outgrowth via binding microRNA-125a in a cellular model of Alzheimer's disease

Zhou,Bingling; Li,Lijuan; Qiu,Xin; Wu,Jiashun; Xu,Lei; Shao,Wei

doi:10.3892/mmr.2020.11203

Long non-coding RNA ANRIL knockdown suppresses apoptosis and pro-inflammatory cytokines while enhancing neurite outgrowth via binding microRNA-125a in a cellular model of Alzheimer's disease

Authors:
- Bingling Zhou
- Lijuan Li
- Xin Qiu
- Jiashun Wu
- Lei Xu
- Wei Shao
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Affiliations: Department of Neurology, Wuhan No.1 Hospital, Wuhan, Hubei 430022, P.R. China
Published online on: June 2, 2020 https://doi.org/10.3892/mmr.2020.11203
Pages: 1489-1497
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effect of the long non-coding RNA antisense non-coding RNA in the INK4 locus (lnc-ANRIL) knockdown on apoptosis, neurite outgrowth and inflammation based on a PC12 cellular Alzheimer's disease (AD) model. A cellular AD model was constructed by treating nerve growth factor stimulated PC12 cells with amyloid β (Aβ) 1-42 and then control knockdown plasmid and lnc-ANRIL knockdown plasmid were transfected in the PC12 cellular AD model as the KD- negative control (NC) group or the AD-ANRIL group respectively. Apoptosis, neurite outgrowth, pro-inflammatory cytokines and microRNA (miR)-125a were assessed. Rescue experiments were conducted by transfecting lnc-ANRIL knockdown plasmid and lnc-ANRIL knockdown plasmid and miR-125a inhibitor in the PC12 cellular AD model as the KD-ANRIL group or KD-ANRIL + KD-miR-125a group respectively. Following transfection, cell apoptosis deccreased while neurite outgrowth increased in the KD-ANRIL group compared with the KD-NC group (all P<0.01). Concerning inflammation, tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, IL-6 and IL-17 were decreased in the KD-ANRIL group compared with the KD-NC group (all P<0.01). miR-125a was negatively regulated by lnc-ANRIL and therefore rescue experiments were subsequently conducted. In the rescue experiments, cell apoptosis was increased while total neurite outgrowth was inhibited in the KD-ANRIL + KD-miR-125a group compared with the KD-ANRIL group (all P<0.01), and TNF-α, IL-1β, IL-6 and IL-17 were increased in the KD-ANRIL + KD-miR-125a group compared with the KD-ANRIL group (all P<0.01). A luciferase reporter assay demonstrated that lnc-ANRIL directly bound miR-125a. lnc-ANRIL knockdown suppressed cell apoptosis and inflammation while promoting neurite outgrowth via binding of miR-125a in AD.

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