Koutsoulidou Andrie, Photiades Marinos, Kyriakides Tassos C, Georgiou Kristia, Prokopi Marianna, Kapnisis Konstantinos, Lusakowska Anna, Nearchou Marianna, Christou Yiolanda, Papadimas George K, Anayiotos Andreas, Kyriakou Kyriakos, Kararizou Evangelia, Zamba Papanicolaou Eleni, Phylactou Leonidas A
Department of Molecular Genetics, Function & Therapy, Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, USA.
Hum Mol Genet. 2017 Sep 1;26(17):3285-3302. doi: 10.1093/hmg/ddx212.
Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy, which is characterised by progressive muscle wasting and the discovery of reliable blood-based biomarkers could be useful for the disease progress monitoring. There have been some reports showing that the presence of specific miRNAs in blood correlates with DM1. In one of these, our group identified four muscle-specific miRNAs, miR-1, miR-133a, miR-133b and miR-206, which correlated with the progression of muscle wasting observed in DM1 patients. The levels of the four muscle-specific miRNAs were elevated in the serum of DM1 patients compared to healthy participants and were also elevated in the serum of progressive muscle wasting DM1 patients compared to disease-stable DM1 patients. The aim of this work was to characterise the ontology of these four muscle-specific miRNAs in the blood circulation of DM1 patients. Here we show that the four muscle-specific miRNAs are encapsulated within exosomes isolated from DM1 patients. Our results show for the first time, the presence of miRNAs encapsulated within exosomes in blood circulation of DM1 patients. More interestingly, the levels of the four exosomal muscle-specific miRNAs are associated with the progression of muscle wasting in DM1 patients. We propose that exosomal muscle-specific miRNAs may be useful molecular biomarkers for monitoring the progress of muscle wasting in DM1 patients. There has been a growing interest regarding the clinical applications of exosomes and their role in prognosis and therapy of various diseases and the above results contribute towards this way.
1型强直性肌营养不良（DM1）是成人发病型肌营养不良最常见的形式，其特征为进行性肌肉萎缩，发现可靠的血液生物标志物可能有助于监测疾病进展。已有一些报告表明血液中特定miRNA的存在与DM1相关。其中一项研究中，我们的团队鉴定出四种肌肉特异性miRNA，即miR-1、miR-133a、miR-133b和miR-206，它们与DM1患者中观察到的肌肉萎缩进展相关。与健康参与者相比，DM1患者血清中这四种肌肉特异性miRNA的水平升高，与疾病稳定的DM1患者相比，进行性肌肉萎缩的DM1患者血清中这些miRNA水平也升高。这项工作的目的是在DM1患者的血液循环中表征这四种肌肉特异性miRNA的本体。在此我们表明，这四种肌肉特异性miRNA包裹在从DM1患者分离的外泌体中。我们的结果首次表明，DM1患者血液循环中的外泌体中存在miRNA。更有趣的是，四种外泌体肌肉特异性miRNA的水平与DM1患者肌肉萎缩的进展相关。我们提出，外泌体肌肉特异性miRNA可能是监测DM1患者肌肉萎缩进展的有用分子生物标志物。人们对外泌体的临床应用及其在各种疾病的预后和治疗中的作用越来越感兴趣，上述结果为此做出了贡献。
