Related Experiment Video
Updated: Sep 10, 2025
Author Spotlight: Exploring Sex-Specific Glial Signatures and Therapeutic Leads for Alzheimer's Disease
Published on: May 20, 2024
MicroRNA-153-3p targets repressor element 1-silencing transcription factor (REST) and neuronal differentiation:
Ruizhi Wang1, Bryan Maloney1, John S Beck2
1Department of Psychiatry, Laboratory of Molecular Neurogenetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Introduction:
Small non-coding microRNAs (miRNAs) play essential roles in Alzheimer's disease (AD) pathogenesis. Repressor element 1-silencing transcription factor (REST) is involved in AD, though its regulation remains unclear.
Methods:
We performed real-time quantitative polymerase chain reaction (qPCR) in autopsied brain tissues to determine miR-153-3p and AD associations. A reporter-based assay measured the activity of REST mRNA 3'-untranslated region (3'-UTR). Induced pluripotent stem cells (iPSC)-derived neurons and human cell lines were applied to determine miR-153-3p regulation of endogenous proteins.
Results:
Elevation of miR-153-3p is associated with a reduced probability of AD, while elevated REST is associated with a greater probability of AD. The 3'-UTR functional assay pinpointed the miR-153-3p binding sites. miR-153-3p treatment reduced REST, amyloid precursor protein (APP), and α-synuclein (SNCA) 3'-UTR activities and protein levels. miR-153-3p treatment altered REST and neuronal differentiation in iPSC-derived neuronal stem cells. RNA-sequencing and proteomics revealed miR-153-3p-associated networks.
Discussion:
miR-153-3p reduces REST, APP, and SNCA expression, pointing toward its therapeutic and biomarker potential in neurodegenerative diseases.
Highlights:
With the increased emphasis on comorbidities of Alzheimer's disease (AD) and other neurodegenerative diseases, we identified that miR-153-3p, as a master regulator, reduced a group of neurodegeneration related proteins: REST, amyloid precursor protein (APP) and α-synuclein (SNCA) levels. The elevation of miR-153-3p levels is associated with reduced probability of AD in posterior cingulate cortex (PCC), while REST, by contrast, is associated with a greater probability of AD. miR-153-3p treatment alters REST protein levels and neuronal differentiation in induced pluripotent stem cells (iPSC) derived neuronal cells. RNA sequencing proteomics and interactome analysis revealed the role of miR-153-3p in axonal guidance.
More Related Videos
09:33Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
10:48Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
Published on: April 12, 2015
Related Concept Videos
01:22MicroRNAs
02:30siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
02:15Experimental RNAi