The long-non-coding RNA NEAT1 is a novel target for Alzheimer's disease progression via miR-124/BACE1 axis

• Published in: Neurological research (New York) Vol. 41; no. 6; p. 489
• Main Authors: Zhao, Mei-Ying, Wang, Gui-Qing, Wang, Ni-Ni, Yu, Qiao-Yan, Liu, Rong-Li, Shi, Wen-Qian
• Format: Journal Article
• Language: English
• Published: England 03.06.2019
• Subjects: Long-non-coding RNAs; miR-`124/BACE1 axis; Alzheimer’s disease; NEAT1; central nervous system
• ISSN: 1743-1328
• DOI: 10.1080/01616412.2018.1548747

Long-non-coding RNAs (lncRNAs) have been involved in central nervous system recently. A number of studies have reported that lncRNA NEAT1 exerts critical roles in neurodegenerative disorder. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been reported to exert function in the accumulation of amyloid-β (Aβ). Moreover, BACE1 acts as a target of miR-124 in the progression of AD. So far, the biological role and underlying mechanisms of NEAT1 and miR-124 in AD remains elusive. The relative NEAT1 and miR-124 expression was examined by qRT-PCR in the tissues and cells line of AD. Cell apoptosis was examined by FACS. Luciferase reporter assay was performed to verify that miR-124 is a direct target of NEAT1, and BACE1 is a downstream target of miR-124. qRT-PCR and western blot analysis were also performed to determinate the BACE1 and the phosphorylation of tau protein. NEAT1 was notably up-regulated and miR-124 was remarkably down-regulated in AD mouse model. Knockdown of NEAT1 or overexpression of miR-124 showed the protective effects on cellular AD model induced by Aβ. Moreover, miR-124 expression could be up- and down-regulated by suppression or overexpression of NEAT1, respectively. In addition, the expression of BACE1 was the potential functional target of miR-124. These findings suggested that NEAT1 might play a vital role in the development of AD by regulating miR-124/BACE1 axis. The present study showed that NEAT1 worked as a regulating factor to promote the development of AD via modulating miR-124/BACE1 axis, which might be considered as a novel target in AD treatment.