{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:36:10Z","timestamp":1788806170669,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["???:81760215"],"award-info":[{"award-number":["???:81760215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Creatine kinase (CK) as a biomarker has long been expected to be replaced by other fluid biomarkers for Duchenne muscular dystrophy (DMD) because it is independent of disease severity. Growing evidence has demonstrated that muscle-specific microRNAs, known as myomiRs, can act as biomarkers for monitoring muscle pathology and disease severity of DMD patients. To gain insights into the relationship between serum myomiRs and clinical assessment, we measured serum levels of miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 in 48 DMD patients by using real-time quantitative reverse transcription polymerase chain reaction. These were then compared with age, muscle strength, muscle functions, CK levels, cardiac manifestations, and mutation types (deletions, duplications, and small mutations). When compared to 53 controls, the expression levels of myomiRs were all significantly elevated (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). The receiver operating characteristic curves of all seven myomiRs reflected marked differences between DMD patients and healthy controls (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). We also showed that serum levels of myomiRs were positively correlated with lower limb distal muscle strength in patients of all age groups. The levels of miR-499, miR-208b, miR-133a, and miR-133b had significant negative correlations with the time to be upright from the supine position (Gowers' time) and the time taken to climb four stairs in DMD patients older than 7 years. Serum levels of miR-1, miR-133a, miR-133b, and miR-499 in patients with cardiac involvement were remarkably higher than those in non-cardiac-involved patients. There was no significant difference in levels of myomiRs between the different mutation groups. Our results indicated that serum myomiRs could be considered as novel biomarkers for monitoring pathology\/pathophysiology of DMD patients. In particular, miR-499, miR-208b, miR-133a, and miR-133b might have the ability to reflect the extent of muscle impairment.<\/jats:p>","DOI":"10.3389\/fneur.2022.921785","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T16:00:02Z","timestamp":1657123202000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Novel miRNA Biomarkers for Patients With Duchenne Muscular Dystrophy"],"prefix":"10.3389","volume":"13","author":[{"given":"Qi","family":"Meng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzi","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/ana.23528","article-title":"Evidence-based path to newborn screening for duchenne muscular dystrophy","volume":"71","author":"Mendell","year":"2012","journal-title":"Ann Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S1474-4422(18)30024-3","article-title":"Diagnosis and management of duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"B3","first-page":"400","article-title":"Creatine kinase: a review of its use in the diagnosis of muscle disease","volume":"88","author":"Gasper","year":"2005","journal-title":"Med Health RI"},{"key":"B4","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1002\/mus.880090905","article-title":"The effect of aerobic exercise on serum creatine kinase activities","volume":"9","author":"Nicholson","year":"1986","journal-title":"Muscle Nerve."},{"key":"B5","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/emmm.201100133","article-title":"MiRNAs as serum biomarkers for duchenne muscular dystrophy","volume":"3","author":"Cacchiarelli","year":"2011","journal-title":"EMBO Mol Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e80263","DOI":"10.1371\/journal.pone.0080263","article-title":"Dystromirs as serum biomarkers for monitoring the disease severity in duchenne muscular dystrophy","volume":"8","author":"Zaharieva","year":"2013","journal-title":"PLoS ONE."},{"key":"B8","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1111\/jnc.12662","article-title":"Serum miR-206 and other muscle-specific microRNAs as non-invasive biomarkers for duchenne muscular dystrophy","volume":"129","author":"Hu","year":"2014","journal-title":"J Neurochem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1038\/mtna.2014.29","article-title":"Circulating muscle-specific miRNAs in duchenne muscular dystrophy patients","volume":"3","author":"Li","year":"2014","journal-title":"Mol Ther Nucleic Acids."},{"key":"B10","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/ptj\/72.2.115","article-title":"Intrarater reliability of manual muscle test (Medical Research Council Scale) grades in Duchenne's Muscular Dystrophy","volume":"72","author":"Florence","year":"1992","journal-title":"Phys Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/mus.880060204","article-title":"Clinical investigation in duchenne dystrophy: 2. Determination of the \u201cpower\u201d of therapeutic trials based on the natural history","volume":"6","author":"Brooke","year":"1983","journal-title":"Muscle Nerve."},{"key":"B12","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.nmd.2011.04.005","article-title":"Electrocardiographic abnormalities in very young Duchenne muscular dystrophy patients precede the onset of cardiac dysfunction","volume":"21","author":"James","year":"2011","journal-title":"Neuromuscular Disorders."},{"key":"B13","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12920-019-0521-8","article-title":"Identification of potential biomarkers for diagnosis of pancreatic and biliary tract cancers by sequencing of serum microRNAs","volume":"12","author":"Kim","year":"2019","journal-title":"BMC Med Genomics."},{"key":"B14","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1471-213X-11-34","article-title":"Expression of miR-1, miR-133a, miR-133b and miR-206 increases during development of human skeletal muscle","volume":"11","author":"Koutsoulidou","year":"2011","journal-title":"BMC Dev Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.cmet.2010.07.008","article-title":"MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin\/nNOS pathway","volume":"12","author":"Cacchiarelli","year":"2010","journal-title":"Cell Metab."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e39","DOI":"10.1038\/mtna.2012.26","article-title":"Expression analysis in multiple muscle groups and serum reveals complexity in the microRNA transcriptome of the mdx mouse with implications for therapy","volume":"1","author":"Roberts","year":"2012","journal-title":"Mol Ther Nucleic Acids."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3960","DOI":"10.1093\/hmg\/ddw237","article-title":"Selective release of muscle-specific, extracellular microRNAs during myogenic differentiation","volume":"25","author":"Coenen-Stass","year":"2016","journal-title":"Hum Mol Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1002\/jcsm.12506","article-title":"Uniform sarcolemmal dystrophin expression is required to prevent extracellular microRNA release and improve dystrophic pathology","volume":"11","author":"van Westering","year":"2019","journal-title":"J Cachexia Sarcopenia Muscle."},{"key":"B19","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1080\/15476286.2019.1582956","article-title":"Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics","volume":"16","author":"Coenen-Stass","year":"2019","journal-title":"RNA Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"684","DOI":"10.3389\/fphys.2018.00684","article-title":"Phenotype-specific response of circulating miRNAs provides new biomarkers of slow or fast muscle damage","volume":"9","author":"Siracusa","year":"2018","journal-title":"Front physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/0092-8674(88)90463-1","article-title":"Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy","volume":"52","author":"Webster","year":"1988","journal-title":"Cell Press."},{"key":"B22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/B978-0-7020-7471-4.00010-0","article-title":"Muscular dystrophies and allied disorders I: duchenne and becker muscular dystrophy","volume-title":"Muscle Biopsy: A Practical Approach","year":"2020"},{"key":"B23","doi-asserted-by":"publisher","first-page":"22","DOI":"10.5414\/NP300889","article-title":"Circulating microRNAs as biomarkers of muscle differentiation and atrophy in ALS","volume":"35","author":"Tasca","year":"2015","journal-title":"Clin Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0220665","DOI":"10.1371\/journal.pone.0220665","article-title":"Cross-sectional study into age-related pathology of mouse models for limb girdle muscular dystrophy types 2D and 2F","volume":"14","author":"Verhaart","year":"2019","journal-title":"PLoS ONE."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e89065","DOI":"10.1371\/journal.pone.0089065","article-title":"MicroRNA-206: a potential circulating biomarker candidate for amyotrophic lateral sclerosis","volume":"9","author":"Toivonen","year":"2014","journal-title":"PLoS ONE."},{"key":"B26","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.nmd.2014.02.005","article-title":"Plasma microRNAs as biomarkers for myotonic dystrophy type 1","volume":"24","author":"Perfetti","year":"2014","journal-title":"Neuromuscul Disord."},{"key":"B27","doi-asserted-by":"publisher","first-page":"38174","DOI":"10.1038\/srep38174","article-title":"Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1","volume":"6","author":"Perfetti","year":"2016","journal-title":"Sci Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0125341","DOI":"10.1371\/journal.pone.0125341","article-title":"Elevated muscle-specific miRNAs in serum of myotonic dystrophy patients relate to muscle disease progress","volume":"10","author":"Koutsoulidou","year":"2015","journal-title":"PLoS ONE."},{"key":"B29","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3390\/diagnostics10090713","article-title":"MiRNAs, myostatin, and muscle MRI imaging as biomarkers of clinical features in Becker Muscular Dystrophy","volume":"10","author":"Marozzo","year":"2020","journal-title":"Diagnostics."},{"key":"B30","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3389\/fneur.2020.00304","article-title":"Longitudinal study of three microRNAs in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy","volume":"11","author":"Trifunov","year":"2020","journal-title":"Front Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"8361237","DOI":"10.1155\/2017\/8361237","article-title":"Serum miRNAs miR-23a, 206, and 499 as potential biomarkers for skeletal muscle atrophy","volume":"2017","author":"Wang","year":"2017","journal-title":"Biomed Res Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0960-8966(96)00357-4","article-title":"Cardiac and respiratory involvement in advanced stage Duchenne muscular dystrophy","volume":"6","author":"Melacini","year":"1996","journal-title":"Neuromuscular Disorders."},{"key":"B33","doi-asserted-by":"publisher","first-page":"700","DOI":"10.3390\/ijms21030700","article-title":"Potential clinical implications of miR-1 and miR-21 in heart disease and cardioprotection","volume":"21","author":"Kura","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"632392","DOI":"10.3389\/fcvm.2021.632392","article-title":"Role of microRNAs in the pathogenesis of coronary artery disease","volume":"8","author":"Ghafouri-Fard","year":"2021","journal-title":"Front Cardiovasc Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"eabn6875","DOI":"10.1126\/scisignal.abn6875","article-title":"Protein tyrosine phosphatase 1B regulates miR-208b-argonaute 2 association and thyroid hormone responsiveness in cardiac hypertrophy","volume":"15","author":"Coulis","year":"2022","journal-title":"Sci Signal"},{"key":"B36","doi-asserted-by":"publisher","first-page":"773314","DOI":"10.3389\/fcvm.2021.773314","article-title":"miR-208a in cardiac hypertrophy and remodeling","volume":"8","author":"Huang","year":"2021","journal-title":"Front Cardiovasc Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13020-022-00615-6","article-title":"Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis","volume":"17","author":"Qi","year":"2022","journal-title":"Chin Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1002\/cbin.11707","article-title":"LncRNA TUG1 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR-133b in myocardial fibrosis after myocardial infarction","volume":"45","author":"Zhang","year":"2021","journal-title":"Cell Biol Int."},{"key":"B39","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/S1474-4422(03)00585-4","article-title":"Dystrophin and mutations: one gene, several proteins, multiple phenotypes","volume":"2","author":"Muntoni","year":"2003","journal-title":"Lancet Neurol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.921785\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T16:00:16Z","timestamp":1657123216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.921785\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":39,"alternative-id":["10.3389\/fneur.2022.921785"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.921785","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]},"article-number":"921785"}}