miR-153-3p参与调控淀粉样前体表达及其在阿尔茨海默病中的生物学意义

Participation of miR-153-3p in regulation of amyloid precursor expression and its biological significance in Alzheimer’s disease

目的研究miR-153-3p与淀粉样前体蛋白(amyloid precursor protein,APP)的靶向关系以及其在阿尔茨海默病(Alzheimer’s disease,AD)发病过程中的生物学意义。方法通过双荧光素酶实验检测miR-153-3p与APP的靶向关系,通过RNA干扰和蛋白免疫印迹实验研究miR-153-3p对APP的表达影响,并研究不同年龄大小APP/PS1双转基因小鼠和不同阶段AD患者体液中miR-153-3p的表达差异。结果miR-153-3p可直接与APP结合并降低其表达。在3月、6月和9月龄的APP/PS1双转基因小鼠海马和脑脊液外泌体中到miR-153-3p表达降低,轻度认知功能损伤(mild cognitive impairment,MCI)和阿茨海默型老年痴呆(dementia of Alzheimer type,DAT)患者的脑脊液外泌体和血清外泌体中miR-153-3p水平低于对照组。结论miR-153-3p可直接降低APP表达,血清外泌体miR-153-3p可能是新的、无创的AD血液生物标记物。

Objective To study the targeting relationship between miR-153-3 p and amyloid precursor protein(APP)and its biological significance in the pathogenesis of Alzheimer’s disease(AD).Methods The targeting relationship between miR-153-3 p and APP was detected by double luciferase assay.The effect of miR-153-3 p on the expression of APP was studied by RNA interference and Western blotting.The expression of miR-153-3 p in body fluids of APP/PS1 double-transgenic mice of different ages and AD patients of different stages was also studied.Results mi R-153-3 p directly bound to APP and reduced its expression.The expression levels of miR-153-3 p were decreased in hippocampus and cerebrospinal fluid exosomes of APP/PS1 double-transgenic mice at 3 months,6 months and 9 months.The expression levels of miR-153-3 p in cerebrospinal fluid exosomes and serum exosomes of mild cognitive impairment(MCI)and dementia of Alzheimer type(DAT)patients were lower than that of the control group.Conclusion mi R-153-3 p can directly reduce the expression of APP.Serum exosome miR-153-3 p could be a new non-invasive blood biomarker for AD.