Meng Qi, Zhang Jiapeng, Zhong Jingzi, Zeng Dan, Lan Dan
Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Neurol. 2022 Jul 6;13:921785. doi: 10.3389/fneur.2022.921785. eCollection 2022.
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 ( < 0.05). The receiver operating characteristic curves of all seven myomiRs reflected marked differences between DMD patients and healthy controls ( < 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.
肌酸激酶（CK）作为一种生物标志物，长期以来一直有望被用于杜氏肌营养不良症（DMD）的其他体液生物标志物所取代，因为它与疾病严重程度无关。越来越多的证据表明，被称为肌微RNA（myomiRs）的肌肉特异性微小核糖核酸可以作为监测DMD患者肌肉病理和疾病严重程度的生物标志物。为了深入了解血清肌微RNA与临床评估之间的关系，我们使用实时定量逆转录聚合酶链反应测定了48例DMD患者血清中miR-1、miR-133a、miR-133b、miR-206、miR-208a、miR-208b和miR-499的水平。然后将这些结果与年龄、肌肉力量、肌肉功能、CK水平、心脏表现和突变类型（缺失、重复和小突变）进行比较。与53名对照相比，肌微RNA的表达水平均显著升高（<0.05）。所有七种肌微RNA的受试者工作特征曲线反映了DMD患者与健康对照之间的显著差异（<0.05）。我们还表明，在所有年龄组的患者中，血清肌微RNA水平与下肢远端肌肉力量呈正相关。在7岁以上的DMD患者中，miR-499、miR-208b、miR-133a和miR-133b的水平与从仰卧位站立的时间（Gowers时间）和爬四级楼梯所需的时间呈显著负相关。有心脏受累的患者血清中miR-1、miR-133a、miR-133b和miR-499的水平明显高于无心脏受累的患者。不同突变组之间肌微RNA水平无显著差异。我们的结果表明，血清肌微RNA可被视为监测DMD患者病理/病理生理学的新型生物标志物。特别是，miR-499、miR-208b、miR-133a和miR-133b可能有能力反映肌肉损伤的程度。
