Comprehensive RNA-sequencing analysis in serum and muscle reveals novel small RNA signatures with biomarker potential for DMD
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- dc.contributor.author Coenen-Stass, Anna M.L.
- dc.contributor.author Sork, Helena
- dc.contributor.author Gatto, Sole
- dc.contributor.author Godfrey, Caroline
- dc.contributor.author Bhomra, Amarjit
- dc.contributor.author Krjutškov, Kaarel
- dc.contributor.author Hart, Jonathan R.
- dc.contributor.author Westholm, Jakub O.
- dc.contributor.author O'Donovan, Liz
- dc.contributor.author Roos, Andreas
- dc.contributor.author Lochmüller, Hanns
- dc.contributor.author Puri, Pier Lorenzo
- dc.contributor.author El Andaloussi, Samir
- dc.contributor.author Wood, Matthew J.A.
- dc.contributor.author Roberts, Thomas C.
- dc.date.accessioned 2019-11-22T08:54:28Z
- dc.date.available 2019-11-22T08:54:28Z
- dc.date.issued 2018
- dc.description.abstract Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their biological relevance is largely unknown. To investigate the relationship between intracellular and extracellular sRNA levels on a global scale, we performed sRNA sequencing in four muscle types and serum from wild-type, dystrophic mdx, and mdx mice in which dystrophin protein expression was restored by exon skipping. Differentially abundant sRNAs were identified in serum (mapping to miRNA, small nuclear RNA [snRNA], and PIWI-interacting RNA [piRNA] loci). One novel candidate biomarker, miR-483, was increased in both mdx serum and muscle, and also elevated in DMD patient sera. Dystrophin restoration induced global shifts in miRNA (including miR-483) and snRNA-fragment abundance toward wild-type levels. Specific serum piRNA-like sRNAs also responded to exon skipping therapy. Absolute miRNA expression in muscle was positively correlated with abundance in the circulation, although multiple highly expressed miRNAs in muscle were not elevated in mdx serum, suggesting that both passive and selective release mechanisms contribute to serum miRNA levels. In conclusion, this study has revealed new insights into the sRNA biology of dystrophin deficiency and identified novel DMD biomarkers.
- dc.format.mimetype application/pdf
- dc.identifier.citation Coenen-Stass AML, Sork H, Gatto S, Godfrey C, Bhomra A, Krjutškov K, Hart JR, Westholm JO, O'Donovan L, Roos A, Lochmüller H, Puri PL, El Andaloussi S, Wood MJA, Roberts TC. Comprehensive RNA-sequencing analysis in serum and muscle reveals novel small RNA signatures with biomarker potential for DMD. Mol Ther Nucleic Acids. 2018; 13:1-15. DOI 10.1016/j.omtn.2018.08.005
- dc.identifier.doi http://dx.doi.org/10.1016/j.omtn.2018.08.005
- dc.identifier.issn 2162-2531
- dc.identifier.uri http://hdl.handle.net/10230/42936
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Mol Ther Nucleic Acids. 2018; 13:1-15
- dc.rights © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Duchenne muscular dystrophy
- dc.subject.keyword Extracellular miRNA
- dc.subject.keyword microRNA
- dc.subject.keyword piRNA
- dc.subject.keyword Small RNA sequencing
- dc.title Comprehensive RNA-sequencing analysis in serum and muscle reveals novel small RNA signatures with biomarker potential for DMD
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion