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

Gaughwin, Philip LU ; Ciesla, Maciej; Lahiri, Nayana; Tabrizi, Sarah J.; Brundin, Patrik LU and Björkqvist, Maria LU (2011) In Human Molecular Genetics 20(11). p.2225-2237
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
20
issue
11
pages
2225 - 2237
publisher
Oxford University Press
external identifiers
  • wos:000290589800013
  • scopus:79956032718
  • pmid:21421997
ISSN
0964-6906
DOI
10.1093/hmg/ddr111
language
English
LU publication?
yes
id
7f013389-4bd0-4b11-be91-59d9bfee343d (old id 1986863)
date added to LUP
2011-07-01 09:20:30
date last changed
2017-11-12 03:11:11
@article{7f013389-4bd0-4b11-be91-59d9bfee343d,
  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.},
  author       = {Gaughwin, Philip and Ciesla, Maciej and Lahiri, Nayana and Tabrizi, Sarah J. and Brundin, Patrik and Björkqvist, Maria},
  issn         = {0964-6906},
  language     = {eng},
  number       = {11},
  pages        = {2225--2237},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease},
  url          = {http://dx.doi.org/10.1093/hmg/ddr111},
  volume       = {20},
  year         = {2011},
}