LncRNA NEAT1 promotes Alzheimer's disease by down regulating micro-27a-3p

Li-Xia Dong; Yan-Yun Zhang; Hai-Lan Bao; Yu Liu; Guo-Wei Zhang; Feng-Mao An

LncRNA NEAT1 promotes Alzheimer's disease by down regulating micro-27a-3p

Am J Transl Res. 2021 Aug 15;13(8):8885-8896. eCollection 2021.

Authors

Li-Xia Dong^{1

2}, Yan-Yun Zhang^{1

2}, Hai-Lan Bao^{1

2}, Yu Liu^{1

2}, Guo-Wei Zhang^{1

2}, Feng-Mao An^{2

3}

Affiliations

¹ College of Nursing, Inner Mongolia University for Nationalities Tongliao 028000, Inner Mongolia Autonomous Region, P. R. China.
² Institute of Dementia, Inner Mongolia University for Nationalities Tongliao, Inner Mongolia, P. R. China.
³ Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System Tongliao, Inner Mongolia, P. R. China.

PMID: 34540002
PMCID: PMC8430163

Abstract

Objective: Alzheimer's disease (AD) is a common neurodegenerative disease. This study was designed to investigate the roles of lncRNA NEAT1/miR-27a-3p axis in AD.

Methods: Amyloid protein was used to treat SH-SY5Y cells and rats to construct AD model. RT-qPCR was used to quantify lncRNA NEAT1 and micro-27a-3p in AD model cells. Western blot was used to determine the β-amyloid-precursor-protein-cleaver-enzyme 1 (BACE1), amyloid, Tau protein and its phosphorylation, Caspase 3 protein and its lytic cell protein and amyloid precursor protein (APP). Flow cytometry was used to detect apoptosis. The cell activity was detected by CCK-8. The lncRNA NEAT1 and miR-27a-3p inhibition or over-expression vectors were constructed. The dual luciferase reporter gene and RNA pull-down assay were used to detect the targeting relationship between lncRNA NEAT1 and micro-27a-3p. The cognitive function of rats was tested by water maze.

Results: After being induced by amyloid protein, lncRNA NEAT1 was up-regulated while micro-27a-3p was down-regulated in SH-SY5Y cells. Apoptosis rate was increased and cell activity was decreased. Amyloid protein, BACE1 protein, APP protein, Tau protein and its phosphorylation, Caspase 3 protein and its lytic cell protein were up-regulated. Down-regulation of lncRNA NEAT1 or up-regulation of micro-27a-3p could reduce cell apoptosis, increase cell activity, down-regulate amyloid protein, BACE1 protein, APP protein, Tau protein and its phosphorylation, and up-regulate caspase 3 protein and its lysate protein. Dual luciferase reporter gene assay and RNA pull-down experiments revealed that micro-27a-3p was the target gene of lncRNA NEAT1. Down-regulation of micro-27a-3p could offset the changes caused by LncRNA NEAT1. AD caused cognitive dysfunction in rats, which was improved by down-regulation of lncRNA NEAT1.

Conclusion: lncRNA NEAT1 regulates the development of AD by down-regulating micro-27a-3p.

Keywords: Alzheimer’s disease; lncRNA NEAT1; miR-27a-3p.