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Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease.

Gaughwin, Philip Michael, Ciesla, Maciej, Lahiri, Nayana, Tabrizi, Sarah J., Brundin, Patrik, Björkqvist, Maria·2011·Human Molecular Genetics
DOI 10.1093/hmg/ddr111
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Abstract

Huntington's disease (HD) is a devastating, neurodegenerative condition, which lacks effective treatment. Normal Huntingtin (HTT) and mutant Huntingtin (mHTT) are expressed in multiple tissues and can alter transcription of microRNAs (miRs). Importantly, miRs are present in a bio-stable form in human peripheral blood plasma and have recently been shown to be useful biomarkers in other diseases. We therefore sought to identify potential miR biomarkers of HD that are present in, and have functional consequences for, neuronal and non-neuronal tissues. In a cell line over-expressing mHTT-Exon-1, miR microarray analysis was used to identify candidate miRs. We then examined their presence and bio-stability in control and HD plasma. We found that miR-34b is significantly elevated in response to mHTT-Exon-1, and its blockade alters the toxicity of mHTT-Exon-1 in vitro. We also show that miR-34b is detectable in plasma from small input volumes and is insensitive to freeze-thaw-induced RNA degradation. Interestingly, miR-34b is significantly elevated in plasma from HD gene carriers prior to symptom onset. This is the first study suggesting that plasma miRs might be used as biomarkers for HD.

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Metadata

Authors
Gaughwin, P. M., Ciesla, M., Lahiri, N., Tabrizi, S. J., Brundin, P., & Björkqvist, M.
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2011-03-19
Volume
20
Issue
11
Pages
2225-2237
ISSN
  • 1460-2083
  • 0964-6906
DOI
10.1093/hmg/ddr111
Cited by
145
References
4
Language
en

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