MicroRNA-101 downregulates Alzheimer's amyloid-β precursor protein levels in human cell cultures and is differentially expressed

Justin M. Long, Debomoy K. Lahiri

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

The full repertoire of regulatory interactions utilized by human cells to control expression of amyloid-β precursor protein (APP) is still undefined. We investigated here the contribution of microRNA (miRNA) to this regulatory network. Several bioinformatic algorithms predicted miR-101 target sites within the APP 3'-untranslated region (3'-UTR). Using reporter assays, we confirmed that, in human cell cultures, miR-101 significantly reduced the expression of a reporter under control of APP 3'-UTR. Mutation of predicted site 1, but not site 2, eliminated this reporter response. Delivery of miR-101 directly to human HeLa cells significantly reduced APP levels and this effect was eliminated by co-transfection with a miR-101 antisense inhibitor. Delivery of a specific target protector designed to blockade the interaction between miR-101 and its functional target site within APP 3'-UTR enhanced APP levels in HeLa. Therefore, endogenous miR-101 regulates expression of APP in human cells via a specific site located within its 3'-UTR. Finally, we demonstrate that, across a series of human cell lines, highest expression of miR-101 levels was observed in model NT2 neurons.

Original languageEnglish (US)
Pages (from-to)889-895
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume404
Issue number4
DOIs
StatePublished - Jan 28 2011

Keywords

  • Aging
  • Alzheimer
  • Amyloid
  • Dementia
  • Neurodegeneration
  • Non-coding RNA
  • Post-transcriptional

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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