MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2

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• 作者：Chunlian Liang ; Hua Zhu ; Yanfeng Xu ; Lan Huang ; Chunmei Ma ; Wei Deng ; Ying Liu ; Chuan Qin ; ^{qinchuan@pumc.edu.cn}
• 关键词：AD ; Alzheimer's disease ; APP ; amyloid precursor protein ; APLP2 ; amyloid precursor-like protein 2 ; UTR ; untranslated region ; miRNAs ; microRNAs ; A尾 ; beta-amyloid peptide ; CNS ; central nervous system ; PD ; Parkinson's disease ; SNCA ; alpha-synuclein ; Bcl-2 ; B
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：21 May, 2012
• 卷：1455
• 期：Complete
• 页码：103-113
• 文件大小：1291 K

摘要

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螖E9 murine model. Moreover, a binding site of miR-153 on APP and APLP2-3鈥睻TR 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尾₄₂ peptides and H₂O_2, the levels of miR-153 varied during time-course leading to corresponding changes of APLP2 protein, indicating A尾 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.