MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression

Jaekwang Kim, Hyejin Yoon, Cristina M. Ramírez, Sang Mi Lee, Hyang Sook Hoe, Carlos Fernández-Hernando, Jungsu Kim

Research output: Contribution to journalArticle

112 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)476-483
Number of pages8
JournalExperimental Neurology
Volume235
Issue number2
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

ATP-Binding Cassette Transporters
Cholesterol
Apolipoproteins
3' Untranslated Regions
MicroRNAs
Amyloid
Alzheimer Disease
Homeostasis
Lipids

Keywords

  • ABCA1
  • Alzheimer's disease
  • Amyloid β
  • Cholesterol
  • Lipid
  • Liver X receptor
  • LXR
  • MicroRNA
  • MiR-106b

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Kim, J., Yoon, H., Ramírez, C. M., Lee, S. M., Hoe, H. S., Fernández-Hernando, C., & Kim, J. (2012). MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression. Experimental Neurology, 235(2), 476-483. https://doi.org/10.1016/j.expneurol.2011.11.010

MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression. / Kim, Jaekwang; Yoon, Hyejin; Ramírez, Cristina M.; Lee, Sang Mi; Hoe, Hyang Sook; Fernández-Hernando, Carlos; Kim, Jungsu.

In: Experimental Neurology, Vol. 235, No. 2, 06.2012, p. 476-483.

Research output: Contribution to journalArticle

Kim, J, Yoon, H, Ramírez, CM, Lee, SM, Hoe, HS, Fernández-Hernando, C & Kim, J 2012, 'MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression', Experimental Neurology, vol. 235, no. 2, pp. 476-483. https://doi.org/10.1016/j.expneurol.2011.11.010
Kim, Jaekwang ; Yoon, Hyejin ; Ramírez, Cristina M. ; Lee, Sang Mi ; Hoe, Hyang Sook ; Fernández-Hernando, Carlos ; Kim, Jungsu. / MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression. In: Experimental Neurology. 2012 ; Vol. 235, No. 2. pp. 476-483.
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