Cited by 36Genetic Neurodegenerative DiseasesMicroRNA in disease regulationAmyotrophic Lateral Sclerosis Research

MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington's disease

Ban, Jae-Jun, Chung, Jin-Young, Lee, Mijung, Im, Wooseok, Kim, Manho·2017·Biochemical and Biophysical Research Communications

Abstract

Huntington's disease (HD) is a fatal genetic disease caused by abnormal aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation decreases cell death of the brain and is a promising therapeutic strategy of HD. MicroRNAs are short non-coding nucleotides which modulate various genes and dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs), we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt aggregation. R6/2-derived NSCs can be differentiated under condition of growth factor deprivation, and the progression of differentiation leads to a decrease of MDR-1 level and efflux function of cells. Immunocytochemistry result also confirmed that mHtt aggregation was increased with differentiation. We transfected miR-27a in the R6/2-derived differentiated NSCs, and examined phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can transport mHtt, protein level was increased by miR-27a transfection. Conversely, knock-down of MDR-1 through MDR-1 siRNA increased mHtt aggregation in vitro. Our results indicate that miR-27a could reduce mHtt level of the HD cell by augmenting MDR-1 function.

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Crossref · 10.1016/j.bbrc.2017.05.040

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  • Several miRNA related therapies were reported for genetic and rare diseases.

    “While many miRNA mimics and antimiRs have been focused on cancer therapies due to their biological roles and properties, several miRNA related therapies were reported for genetic and rare diseases.[237, 239]”

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Authors
Ban, J.-J., Chung, J.-Y., Lee, M., Im, W., & Kim, M.
Affiliations
  • Seoul National University (KR)
  • Kangwon National University (KR)
Corresponding author
  • Im, Wooseok
  • Kim, Manho
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2017-06
Volume
488
Issue
2
Pages
316-321
ISSN
0006-291X (ISSN-L)
OpenAlex
W2612627552
Cited by
36
References
43
Citations by year
2026: 2 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 6
FWCI
2.15
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation of Korea (NRF)
  • Ministry of Science, ICT & Future Planning (2016M3C7A1914002)
  • SNUH (03-2016-0340)
  • National Research Foundation of Korea (2015R1D1A1A01060056)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
Huntington's disease, mutant huntingtin aggregation, miR-27a, microRNA, multidrug resistance protein 1, MDR1, R6/2 mouse model, drug efflux, gene knockdown, therapeutic target
MeSH terms
Huntingtin Protein, Animals, Disease Models, Animal, Huntington Disease, Mice, Inbred C57BL, MicroRNAs, Mice, Protein Aggregates

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