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Multi-Omics Identif...
Multi-Omics Identifies Circulating miRNA and Protein Biomarkers for Facioscapulohumeral Dystrophy
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Heier, C. R. (author)
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Zhang, A. P. (author)
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Nguyen, N. Y. (author)
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Tully, C. B. (author)
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Panigrahi, A. (author)
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Gordish-Dressman, H. (author)
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Pandey, S. N. (author)
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Guglieri, M. (author)
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Ryan, M. M. (author)
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Clemens, P. R. (author)
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Thangarajh, M. (author)
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Webster, R. (author)
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Smith, E. C. (author)
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Connolly, A. M. (author)
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McDonald, C. M. (author)
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Karachunski, P. (author)
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- Tulinius, Mar, 1953 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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Harper, A. (author)
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Mah, J. K. (author)
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Fiorillo, A. A. (author)
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Chen, Y. W. (author)
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(creator_code:org_t)
- 2020-11-19
- 2020
- English.
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In: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 10:4
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https://www.mdpi.com...
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Subject headings
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- The development of therapeutics for muscle diseases such as facioscapulohumeral dystrophy (FSHD) is impeded by a lack of objective, minimally invasive biomarkers. Here we identify circulating miRNAs and proteins that are dysregulated in early-onset FSHD patients to develop blood-based molecular biomarkers. Plasma samples from clinically characterized individuals with early-onset FSHD provide a discovery group and are compared to healthy control volunteers. Low-density quantitative polymerase chain reaction (PCR)-based arrays identify 19 candidate miRNAs, while mass spectrometry proteomic analysis identifies 13 candidate proteins. Bioinformatic analysis of chromatin immunoprecipitation (ChIP)-seq data shows that the FSHD-dysregulated DUX4 transcription factor binds to regulatory regions of several candidate miRNAs. This panel of miRNAs also shows ChIP signatures consistent with regulation by additional transcription factors which are up-regulated in FSHD (FOS, EGR1, MYC, and YY1). Validation studies in a separate group of patients with FSHD show consistent up-regulation of miR-100, miR-103, miR-146b, miR-29b, miR-34a, miR-454, miR-505, and miR-576. An increase in the expression of S100A8 protein, an inflammatory regulatory factor and subunit of calprotectin, is validated by Enzyme-Linked Immunosorbent Assay (ELISA). Bioinformatic analyses of proteomics and miRNA data further support a model of calprotectin and toll-like receptor 4 (TLR4) pathway dysregulation in FSHD. Moving forward, this panel of miRNAs, along with S100A8 and calprotectin, merit further investigation as monitoring and pharmacodynamic biomarkers for FSHD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- FSHD
- biomarkers
- miRNA
- proteomics
- calprotectin
- dystrophy
- muscle
- girdle muscular-dystrophy
- microrna expression
- serum biomarkers
- dux4
- expression
- plasma micrornas
- smchd1 mutation
- candidate gene
- DNA
- elements
- diagnosis
- d4z4
- Health Care Sciences & Services
- General & Internal Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Heier, C. R.
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Zhang, A. P.
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Nguyen, N. Y.
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Tully, C. B.
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Panigrahi, A.
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Gordish-Dressman ...
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show more...
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Pandey, S. N.
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Guglieri, M.
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Ryan, M. M.
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Clemens, P. R.
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Thangarajh, M.
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Webster, R.
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Smith, E. C.
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Connolly, A. M.
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McDonald, C. M.
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Karachunski, P.
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Tulinius, Mar, 1 ...
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Harper, A.
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Mah, J. K.
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Fiorillo, A. A.
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Chen, Y. W.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Journal of Perso ...
- By the university
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University of Gothenburg