BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs
BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs
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BACE1-AS 通过隔离 BACE1 靶向 miRNA 来防止 BACE1 mRNA 降解
DOI：
10.1016/j.jchemneu.2019.04.001
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发表时间：
2019-07-01
影响因子：
2.8
通讯作者：
Liu, Houqi
中科院分区：
文献类型：
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作者：
Zeng, Tao;Ni, Haitao;Liu, Houqi
异常长链非编码RNA（lncRNA）和微小RNA（miRNAs）参与阿尔茨海默病（AD）的病理生理过程。然而，目前还不清楚这两种类型的非编码RNA是否在功能上相互作用，以及哪些因子介导了AD中的这些相互作用。β-分泌酶1（BACE 1）是负责淀粉样斑块形成的酶，淀粉样斑块形成是AD的核心病理特征。lncRNA BACE 1-AS和一些miRNA参与了BACE 1的调节。在这项研究中，我们发现BACE 1-AS与BACE 1共享许多miRNA响应元件。BACE 1-AS的过表达导致靶向BACE 1的miRNA的抑制，从而防止BACE 1 mRNA被降解。BACE 1-AS的敲除增加了这些miRNA的水平，从而降低了BACE 1的表达。因此，BACE 1-AS作为竞争性内源RNA（ceRNA）发挥功能。我们的研究结果也加深了对BACE 1-AS调控BACE 1的理解。除了通过形成RNA双链体增加BACE 1 mRNA的稳定性外，BACE 1-AS还可以通过充当ceRNA间接调节BACE 1。因此，我们认为BACE 1作为一种ceRNA发挥作用，并通过与AD病理生理学中的蛋白质编码基因、lncRNA和miRNAs的相关性形成网络。
Abnormal long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participate in the pathophysiology of Alzheimer's disease (AD). However, it remains unclear whether these two types of noncoding RNAs functionally interact and which factors mediate these interactions in AD. beta-secretase 1 (BACE1) is the enzyme responsible for amyloid plaque formation, which is a central pathological feature of AD. The lncRNA BACE1-AS and some miRNAs have been implicated in the regulation of BACE1. In this study, we reveal that BACE1-AS shares many miRNA-response elements with BACE1. The overexpression of BACE1-AS results in the repression of miRNAs that target BACE1, thus preventing BACE1 mRNA from being degraded. The knockdown of BACE1-AS increases the levels of these miRNAs, thereby reducing the expression of BACE1. Thus, BACE1-AS functions as a competing endogenous RNA (ceRNA). Our results also deepen the understanding of the regulation of BACE1 by BACE1-AS. In addition to increasing the stability of BACE1 mRNA through the formation of RNA duplexes, BACE1-AS can regulate BACE1 indirectly by acting as a ceRNA. Therefore, we propose that BACE1 functions as a ceRNA and forms a network through its associations with protein-coding genes, lncRNAs and miRNAs in the pathophysiology of AD.