微小RNA-146a抑制低密度脂蛋白受体相关蛋白2的翻译并导致阿尔茨海默病中的细胞凋亡。
MicroRNA-146a represses LRP2 translation and leads to cell apoptosis in Alzheimer's disease.
作者信息
Zhang Bei, Wang Li-Ling, Ren Ru-Jing, Dammer Eric B, Zhang Yong-Fang, Huang Yue, Chen Sheng-Di, Wang Gang
机构信息
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China.
Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, China.
出版信息
FEBS Lett. 2016 Jul;590(14):2190-200. doi: 10.1002/1873-3468.12229. Epub 2016 Jul 8.
MicroRNA regulation of transcript expression has been reported in patients with Alzheimer's disease (AD). Here, we investigate the role of microRNA-146a (miRNA-146a), a brain-enriched miRNA, which is upregulated in AD patients. Through analysis of predicted targets of miRNA-146a, low-density lipoprotein receptor-related protein-2 (Lrp2), a member of the LDLR family that is known to play a protective role in AD, was identified. Overexpression of miRNA-146a in SH-SY5Y cells significantly decreased Lrp2 expression, resulting in a reduction of Akt activation and induction of proapoptotic caspase-3, thereby increasing cell apoptosis. Thus, specific miRNA-146a regulation may contribute to AD by downregulating the Lrp2/Akt pathway.
已有报道称，阿尔茨海默病（AD）患者存在微小RNA对转录本表达的调控作用。在此，我们研究了微小RNA-146a（miRNA-146a）的作用，它是一种在大脑中高度富集的微小RNA，在AD患者中呈上调状态。通过分析miRNA-146a的预测靶点，我们鉴定出低密度脂蛋白受体相关蛋白2（Lrp2），它是低密度脂蛋白受体（LDLR）家族的成员之一，已知在AD中发挥保护作用。在SH-SY5Y细胞中过表达miRNA-146a可显著降低Lrp2的表达，导致Akt激活减少并诱导促凋亡的半胱天冬酶-3，从而增加细胞凋亡。因此，特定的miRNA-146a调控可能通过下调Lrp2/Akt途径而导致AD。
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