title: MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression.
abstract: 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 β (Aβ) levels. Since ABCA1 has an unusually long 3' untranslated region, we investigated whether microRNAs could regulate ABCA1 expression. We identified miR-106b as a novel regulator of ABCA1 expression and Aβ metabolism. miR-106b significantly decreased ABCA1 levels and impaired cellular cholesterol efflux in neuronal cells. Furthermore, miR-106b dramatically increased levels of secreted Aβ by increasing Aβ production and preventing Aβ clearance. Alterations in Aβ production and clearance were rescued by expression of miR-106b-resistant ABCA1. Taken together, our data suggest that miR-106b affects Aβ metabolism by suppressing ABCA1 expression.
authors: Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Jaekwang
authors: J
authors: Kim
authors: Hyejin
authors: H
authors: Yoon
authors: Cristina M
authors: CM
authors: Ramírez
authors: Sang-Mi
authors: SM
authors: Lee
authors: Hyang-Sook
authors: HS
authors: Hoe
authors: Carlos
authors: C
authors: Fernández-Hernando
authors: Jungsu
authors: J
authors: Kim
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D002784:Cholesterol