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

作者：Long Justin M; Lahiri Debomoy K^*

来源：Biochemical and Biophysical Research Communications, 2011, 404(4): 889-895.

DOI：10.1016/j.bbrc.2010.12.053

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

The full repertoire of regulatory interactions utilized by human cells to control expression of amyloid-beta 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.

• 出版日期2011-1-28