[1]严钢莉 黎逢光 李朝武 聂海岭.MicroRNA-9靶向BACE1参与Alzheimer病发生发展的机制研究[J].卒中与神经疾病杂志,2019,26(02):135-139.[doi:10.3969/j.issn.1007-0478.2019.02.001]
　Yan Gangli,Li Fengguang,Li Chaowu,et al.The downregulaton of microRNA-9 promotes Alzheimer's disease Via targeting BACE1[J].Stroke and Nervous Diseases,2019,26(02):135-139.[doi:10.3969/j.issn.1007-0478.2019.02.001]
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MicroRNA-9靶向BACE1参与Alzheimer病发生发展的机制研究()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第26卷
期数:
2019年02期
页码:
135-139
栏目:
论 著
出版日期:
2019-04-20

文章信息/Info

Title:
The downregulaton of microRNA-9 promotes Alzheimer's disease Via targeting BACE1
文章编号:
1007-0478(2019)02-0135-05
作者:
严钢莉 黎逢光 李朝武 聂海岭
430010 武汉,中部战区总医院汉口院区神经内科[严钢莉 黎逢光(通信作者)李朝武 聂海岭]
Author(s):
Yan Gangli; Li Fengguang; Li Chaowu; et al.
Department of Neurology,The Chinese PLA 161th Hospital,Wuhan 430012
关键词:
Alzheimer's 病 miR-9 BACE1
Keywords:
Alzheimer's disease miR-9 BACE1
分类号:
R742
DOI:
10.3969/j.issn.1007-0478.2019.02.001
文献标志码:
A
摘要:
目的 探讨microRNA-9(miR-9)靶向BACE1参与Alzheimer病(AD)发生发展的机制。方法 选取2013年5月-2015年5月解放军第161医院收治的AD患者23例,以血管性痴呆(Vascular dementia,VD)21例和颅内感染患者(intracranial infection,ICI)20例为对照组,比较3组患者脑脊液中miR-9、BACE1和APP的表达水平; 然后用荧光素酶报告系统验证miR-9与BACE1之间的靶向关系; 最后将miR-9 mimics转染入SH-SY5Y 细胞,qRT-PCR和Western Bolt检测BACE1和APP的mRNA和蛋白表达水平。结果 与VD和ICI组比较,AD患者脑脊液中miR-9表达水平下降,BACE1和APP表达水平增高,AD患者脑脊液中miR-9表达水平与BACE1表达水平呈负相关; BACE1为miR-9的功能靶基因; miR-9可靶向BACE1参与调控SH-SY5Y细胞APP表达。结论 miR-9可靶向BACE1参与AD的发生发展。
Abstract:
ObjectiveTo investigate the effects of microRNA-9( miR-9)Via targeting Beta-site Amyloid precursor protein Cleaving Enzyme(BACE1)on Alzheimer's disease(AD).Methods 23 patients with AD(AD group)and 21 patients with Vascular dementia(VD)(VD group)(the control group),20 patients with intracranial infection(ICI)( ICI group)(the control group)were enrolled in our hospital from May 2013 to May 2015.The expression levels of miR-9,BACE1 and APP in CSF of AD、VD and ICI were detected and compared in three groups.Then wild-type and mutant luciferase reporter plasmids were constructed according to the predicted miR-9 binding site on the 3'-UTR of the BACE1 mRNA and transfected into human embryonic kidney 293 tool cells(HEK293T)to determine the targeting relationship of miR-9 and BACE1.The regulation effects of miR-9 on the BACE1 and APP expression level in human heuroblastoma SH-SY5Y cells were determined.Results Compared with VD group and ICI group,the expression levels of miR-9 in CSF of AD group,the expression levels of BACE1 and APP in CSF of AD group were increased,the expression level of miR-9 was negatively relation with the expression level of BACE1 in CSF of AD.And luciferase reporter assay demonstrated that miR-9 was shown to specifically bind to the 3'-UTR of BACE1.Further miR-9-mimic SH-SY5Y cells showed significantly lower BACE1 mRNA and protein expression levels and APP accumulation than those of matching negative control and non-transfected cells.Conclusion MiR-9 was down-regulated in an association with the up-regulation of BACE1 and APP accumulation in AD CSF,and it could reduce the BACE1 expression level,and APP accumulation in vitro by targeting BACE1.These finding suggested that miR-9 played an important role in the process of AD via targeting BACE1 and might be an new therapeutic molecular target for AD.

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备注/Memo

备注/Memo:
基金项目:武汉中青年医学骨干人才培养工程(2018); 全军医学科技青年培育计划(批准号17QNP050) (2018-05-11收稿)
更新日期/Last Update: 2019-04-20