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长链非编码RNA EBF3-AS促进阿尔茨海默病中的神经元凋亡。

Long Noncoding RNA EBF3-AS Promotes Neuron Apoptosis in Alzheimer's Disease.

作者信息

Gu Cheng, Chen Cheng, Wu Ruipeng, Dong Tong, Hu Xiaojuan, Yao Yuping, Zhang Yi

机构信息

1 Department of Neurology, Gansu Provincial Hospital , Lanzhou, China .

2 Department of Galactophore, The First Hospital of Lanzhou University , Lanzhou, China .

出版信息

DNA Cell Biol. 2018 Mar;37(3):220-226. doi: 10.1089/dna.2017.4012. Epub 2018 Jan 3.

Abstract

Alzheimer's disease (AD) is the most common form of dementia; its pathophysiological mechanism remains unclear. Long noncoding RNAs (lncRNAs) play key roles in AD. lncRNA EBF3-AS has been found dysregulated in AD, which is abundantly expressed in the brain. The aim of this study was to investigate the role of EBF3-AS in AD. Results showed that the expressions of lncRNA EBF3-AS and EBF3 (early B cell factor 3) were upregulated in hippocampus of APP/PS1 mice (AD model mice). EBF3-AS knockdown by siRNA inhibited the apoptosis induced by Aβ and okadaic acid (OA) in SH-SY5Y. The expression of EBF3 was downregulated in Aβ- and OA-treated SH-SY5Y, which was reversed by EBF3-AS knockdown. EBF3 knockdown can reverse the Aβ-induced apoptosis in SH-SY5Y. These results revealed that lncRNA EBF3-AS promoted neuron apoptosis in AD, and involved in regulating EBF3 expression. EBF3-AS may be a new therapeutic target for treatment of AD.

摘要

阿尔茨海默病(AD)是最常见的痴呆形式;其病理生理机制尚不清楚。长链非编码RNA(lncRNAs)在AD中起关键作用。已发现lncRNA EBF3-AS在AD中表达失调,它在大脑中大量表达。本研究的目的是探讨EBF3-AS在AD中的作用。结果显示,lncRNA EBF3-AS和EBF3(早期B细胞因子3)在APP/PS1小鼠(AD模型小鼠)海马中的表达上调。通过小干扰RNA(siRNA)敲低EBF3-AS可抑制Aβ和冈田酸(OA)诱导的SH-SY5Y细胞凋亡。在Aβ和OA处理的SH-SY5Y细胞中,EBF3的表达下调,而敲低EBF3-AS可使其逆转。敲低EBF3可逆转Aβ诱导的SH-SY5Y细胞凋亡。这些结果表明,lncRNA EBF3-AS促进AD中的神经元凋亡,并参与调节EBF3表达。EBF3-AS可能是治疗AD的一个新的治疗靶点。

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