Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2011
Språk
Engelska
Sidor
2225-2237
Publikation/Tidskrift/Serie
Human Molecular Genetics
Volym
20
Issue
11
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Medical Genetics
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0964-6906