title: Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease.
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.
authors.affiliation: Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, S-221 84 Lund, Sweden.
authors.forename: Philip Michael
authors.initials: PM
authors.lastname: Gaughwin
authors.forename: Maciej
authors.initials: M
authors.lastname: Ciesla
authors.forename: Nayana
authors.initials: N
authors.lastname: Lahiri
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.forename: Patrik
authors.initials: P
authors.lastname: Brundin
authors.forename: Maria
authors.initials: M
authors.lastname: Björkqvist
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005091:Exons; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000097:blood / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C522425:MIRN34 microRNA, human; D035683:MicroRNAs