MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington's disease
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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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]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [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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