miR-106b impairs cholesterol efflux and increases A尾 levels by repressing ABCA1 expression

详细信息	查看全文 | 推荐本文 |

• 作者：Jaekwang Kim^a ; Hyejin Yoon^a ; Cristina M. Ramí ; rez^b ; Sang-Mi Lee^c ; Hyang-Sook Hoe^c ; Carlos Ferná ; ndez-Hernando^b ; Jungsu Kim^a ; ^{kimj@neuro.wustl.edu}
• 关键词：ABCA1 ; ATP-binding cassette transporter A1 ; AD ; Alzheimer's disease ; A尾 ; amyloid-尾 ; APP ; amyloid precursor protein ; ApoA-I ; apolipoprotein A1 ; ApoE ; apolipoprotein E ; BACE1 ; 尾-site APP-cleaving enzyme1 ; CTF尾 ; C-terminal fragment 尾 ; HDL ; high-density
• 刊名：Experimental Neurology
• 出版年：2012
• 期刊代码：78_00144886
• 类别：neu
• 出版时间：June, 2012
• 卷：235
• 期：2
• 页码：476-483
• 文件大小：787 K

摘要

ATP-binding cassette transporter A1 (ABCA1) is a cholesterol transporter that transfers excess cellular cholesterol onto lipid-poor apolipoproteins. Given its critical role in cholesterol homeostasis, ABCA1 has been studied as a therapeutic target for Alzheimer's disease. Transcriptional regulation of ABCA1 by liver X receptor has been well characterized. However, whether ABCA1 expression is regulated at the posttranscriptional level is largely unknown. Identification of a novel pathway that regulates ABCA1 expression may provide new strategy for regulating cholesterol metabolism and amyloid 尾 (A尾) levels. Since ABCA1 has an unusually long 3鈥?untranslated region, we investigated whether microRNAs could regulate ABCA1 expression. We identified miR-106b as a novel regulator of ABCA1 expression and A尾 metabolism. miR-106b significantly decreased ABCA1 levels and impaired cellular cholesterol efflux in neuronal cells. Furthermore, miR-106b dramatically increased levels of secreted A尾 by increasing A尾 production and preventing A尾 clearance. Alterations in A尾 production and clearance were rescued by expression of miR-106b-resistant ABCA1. Taken together, our data suggest that miR-106b affects A尾 metabolism by suppressing ABCA1 expression.