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首页> 外文期刊>Journal of chemical neuroanatomy >BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs
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BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs

机译：Bace1-例如通过Bace1靶向miRNA的封存来防止Bace1 mRNA降解

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摘要

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.
机译：长期无量化RNA（LNCRNA）和MicroRNA（miRNA）参与阿尔茨海默病的病理生理学（AD）。然而，仍然不清楚这两种类型的非编码RNA在功能上相互作用，以及哪些因素介导广告中的这些相互作用。 β-分泌酶1（Bace1）是负责淀粉样蛋白斑块形成的酶，这是AD的中心病理特征。 LNCRNA Bace1-AS和一些miRNA在Bace1的调节中涉及。在这项研究中，我们揭示了Bace1-与Bace1的许多miRNA响应元素一样分享。 Bace1的过表达 - 结果在抑制靶向Bace1的miRNA，从而防止Bace1 mRNA降解。 Bace1的敲低 - 增加了这些miRNA的水平，从而减少了Bace1的表达。因此，Bace1-作为竞争内源性RNA（Cerna）的功能。我们的结果也深化了对Bace1的监管的理解。除了通过形成RNA双链体的形成，Bace1-AS可以通过作为Cerna间接调节Bace1之外。因此，我们提出了Bace1用作Cerna，并通过其与蛋白质编码基因，LNCRNA和MiRNA的关联形成网络的网络。

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  • 来源
    《Journal of chemical neuroanatomy》 |2019年第2019期|共10页
  • 作者

    Zeng Tao; Ni Haitao; Yu Yue; Zhang Mingke; Wu Minjuan; Wang Qiaoling; Wang Liujun; Xu Sha; Xu Zhenyu; Xu Chen; Xiong Jun; Jiang Junfeng; Luo Yan; Wang Yue; Liu Houqi;

  • 作者单位

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Changhai Hosp Dept Thyoid &

    Breast Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Shanghai Jiao Tong Univ Sch Med Ruijin Hosp 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

    Second Mil Med Univ Res Ctr Dev Biol 800 Xiangyin Rd Shanghai 200433 Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

    Alzheimer's disease; BACE1; BACE1-AS; beta-amyloid (A beta); Long noncoding RNA (lncRNA);

    机译：阿尔茨海默病;Bace1;Bace1-AS;β-淀粉样蛋白（β）;长的非编码RNA（LNCRNA）;

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