MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2
MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2
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DOI：
10.1016/j.brainres.2011.10.051
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发表时间：
2012-05-21
期刊：
影响因子：
2.9
通讯作者：
Qin, Chuan
中科院分区：
文献类型：
--
作者：
Liang, Chunlian;Zhu, Hua;Qin, Chuan
淀粉样前体蛋白（APP）的表达增加是阿尔茨海默病（AD）的重要危险因素。淀粉样蛋白受体样蛋白2（APLP 2），APP的同源物，也被认为是参与AD的发病机制。越来越多的证据表明microRNA对AD相关基因的调控作用。在此，我们发现在APPswe/PS Delta E9小鼠模型中，miR-153的水平在AD的早期和晚期显著降低。此外，通过荧光素酶测定，分别鉴定了miR-153在APP和APLP 2 - 3 'UTR上的结合位点。功能获得和丧失实验表明，miR-153抑制APP和APLP 2的表达。利用miR-153转基因小鼠模型，证实miR-153在体内下调APP和APLP 2蛋白的表达。此外，miR-153和APP/APLP 2在脑发育过程中的表达模式密切相关，表明miR-153对这两个基因具有生理调节作用。在用A β（42）肽和H2 O2处理的神经元细胞系中，miR-153的水平在时间过程中变化，导致APLP 2蛋白的相应变化，表明A β肽和氧化应激影响miR-153的表达。因此，miR-153有助于APP/APLP 2的转录后调节，表明miR-153在神经病理条件中的可能作用。(C)出版社：Elsevier B. V.
Increased expression of the amyloid precursor protein (APP) is a crucial risk factor of Alzheimer's disease (AD). Amyloid precursor-like protein 2 (APLP2), a homologue of APP, is also suggested to participate in AD pathogenesis. Accumulating evidence suggest the regulatory role of microRNA on AD-related genes. Here we showed that the levels of miR-153 were significantly decreased at early- and late-stage of AD in APPswe/PS Delta E9 murine model. Moreover, a binding site of miR-153 on APP and APLP2-3'UTR was identified, respectively, by luciferase assay. Gain and loss of function experiments demonstrated that miR-153 suppressed the expression of APP and APLP2. Using miR-153 transgenic mouse model, we testified that miR-153 downregulated the expression of APP and APLP2 protein in vivo. Furthermore, closely related expression patterns of miR-153 and APP/APLP2 during brain development indicated a physiological regulation role of miR-153 on the two genes. In a neuronal cell line treated with A beta(42) peptides and H2O2, the levels of miR-153 varied during time-course leading to corresponding changes of APLP2 protein, indicating A beta peptides and oxidative stress influence the expression of miR-153. Thus, miR-153 contributes to post-transcriptional regulation of APP/APLP2, suggesting a possible role for miR-153 in neuro-pathological conditions. (C) 2011 Published by Elsevier B.V.