Circulating Muscle-specific miRNAs in Duchenne Muscular Dystrophy Patients.

Circulating Muscle-specific miRNAs in Duchenne Muscular Dystrophy Patients.
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杜氏肌营养不良症患者的循环肌肉特异性 miRNA

DOI:
10.1038/mtna.2014.29
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发表时间:
2014-07-22
期刊:
Molecular therapy. Nucleic acids
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其他
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具有诊断价值和预后应用的非侵入性生物标志物长期以来一直期望取代杜氏肌营养不良症(DMD)患者的肌肉活检。越来越多的证据表明,循环microRNA是评估病理生理状态的生物标志物。我们发现,DMD患者血清中6种肌肉特异性miRNAs(miR-1/206/133/499/208 a/208 b,也称为myomiRs)的水平均升高(P< 0.01)。循环miR-206、miR-499、miR-208 b和miR-133水平的受试者工作特征曲线反映了Becker肌营养不良症(BMD)和DMD患者之间的强烈分离(P< 0.05)。miR-206、miR-499和miR-208 b水平与DMD患者(2-6岁)的年龄和IIc型肌纤维含量呈正相关,表明它们可能代表疾病的阶段以及再生过程。miR-499和miR-208 b水平与DMD患者(>6岁)的慢纤维和快纤维含量相关,可能反映DMD患者慢纤维和快纤维的比例。成纤维细胞生长因子、转化生长因子-β和肿瘤坏死因子-α可影响myomiRs的分泌,提示循环myomiRs可能反映细胞因子和生长因子对肌肉退变和再生的影响。总的来说,我们的数据表明,循环myomiR可以作为DMD诊断和疾病进展的有希望的生物标志物。
Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for Duchenne muscular dystrophy (DMD) patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the serum levels of six muscle-specific miRNAs (miR-1/206/133/499/208a/208b, also known as myomiRs) were all elevated in DMD patients (P< 0.01). The receiver operating characteristic curves of circulating miR-206, miR-499, miR-208b, and miR-133 levels reflected strong separation between Becker's muscular dystrophy (BMD) and DMD patients (P< 0.05). miR-206, miR-499, and miR-208b levels were positively correlated with both age and type IIc muscle fiber content in DMD patients (2–6 years), indicating that they might represent the stage of disease as well as the process of regeneration. miR-499 and miR-208b levels were correlated with slow and fast fiber content and might reflect the ratio of slow to fast fibers in DMD patient (>6 years). Fibroblast growth factor, transforming growth factor-β, and tumor necrosis factor-α could affect the secretion of myomiRs, suggesting that circulating myomiRs might reflect the effects of cytokines and growth factors on degenerating and regenerating muscles. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for DMD diagnosis and disease progression.
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