miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement
Open accessAbstract
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington's disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. METHODS: We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 HD gene positive, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. RESULTS: We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to processes relating to nervous system development and transcriptional regulation. CONCLUSIONS: These results demonstrate that miRNA expression in cortical BA9 provides insight into striatal involvement and support a role for these miRNAs, particularly miR-10b-5p, in HD pathogenicity. The miRNAs identified in our studies of postmortem brain tissue may be detectable in peripheral fluids and thus warrant consideration as accessible biomarkers for disease stage, rate of progression, and other important clinical characteristics of HD.
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- Authors
- Hoss, A. G., Labadorf, A., Latourelle, J. C., Kartha, V. K., Hadzi, T. C., Gusella, J. F., MacDonald, M. E., Chen, J.-F., Akbarian, S., Weng, Z., Vonsattel, J. P., & Myers, R. H.
- Affiliations
- Boston University (US)
- Harvard University (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Massachusetts Chan Medical School (US)
- NewYork–Presbyterian Hospital (US)
- Corresponding author
- Myers, Richard H
- ORCID
- Venue
- BMC Medical Genomics
- Published
- 2015-03-01
- Volume
- 8
- Issue
- 1
- Pages
- 10-10
- ISSN
- 1755-8794 (ISSN-L)
- PMC
- PMC4349621
- OpenAlex
- W2102648007
- Semantic Scholar
- 0e54f8e987daaf026db58f607b6699cc300f019e
- Cited by
- 151
- References
- 59
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 17 · 2022: 19 · 2021: 19 · 2020: 17 · 2019: 13 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 6 · 2014: 1
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Medical Genomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by)
- Funders
- McLean Hospital
- National Institutes of Health
- National Institute of Mental Health (P50MH096890)
- National Institute of Neurological Disorders and Stroke (R01NS073947, R21NS076958, R01NS032765, U24NS072026)
- 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, miR-10b-5p, microRNA expression, age of onset, prefrontal cortex, CAG repeat expansion, miR-196a-5p, miR-106a-5p, miRNA target genes, neurodegeneration, disease progression biomarkers, trinucleotide repeats
- MeSH terms
- Adult, Aged, Brain, Cerebral Cortex, Corpus Striatum, Female, Gene Expression Regulation, Humans, Huntington Disease, Male, Middle Aged, Linear Models, Age of Onset, Disease Progression, Gene Expression Profiling, MicroRNAs, High-Throughput Nucleotide Sequencing
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