Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, Italy.
J Cell Mol Med. 2022 Sep;26(17):4678-4685. doi: 10.1111/jcmm.17462. Epub 2022 Jul 26.
Becker muscular dystrophy (BMD) is an X-linked neuromuscular disorder due to mutation in the DMD gene, encoding dystrophin. Despite a wide clinical variability, BMD is characterized by progressive muscle degeneration and proximal muscle weakness. Interestingly, a dysregulated expression of muscle-specific microRNAs (miRNAs), called myomirs, has been found in patients affected with muscular dystrophies, although few studies have been conducted in BMD. We analysed the serum expression levels of a subset of myomirs in a cohort of 29 ambulant individuals affected by BMD and further classified according to the degree of alterations at muscle biopsy and in 11 age-matched healthy controls. We found a significant upregulation of serum miR-1, miR-133a, miR-133b and miR-206 in our cohort of BMD patients, supporting the role of these miRNAs in the pathophysiology of the disease, and we identified serum cut-off levels discriminating patients from healthy controls, confiming the potential of circulating miRNAs as promising noninvasive biomarkers. Moreover, serum levels of miR-133b were found to be associated with fibrosis at muscle biopsy and with patients' motor performances, suggesting that miR-133b might be a useful prognostic marker for BMD patients. Taken together, our data showed that these serum myomirs may represent an effective tool that may support stratification of BMD patients, providing the opportunity of both monitoring disease progression and assessing the treatment efficacy in the context of clinical trials.
贝克肌营养不良症(BMD)是一种 X 连锁神经肌肉疾病,由 DMD 基因突变引起,该基因编码肌营养不良蛋白。尽管临床表现存在广泛的变异性,但 BMD 的特征是进行性肌肉退化和近端肌肉无力。有趣的是,在患有肌肉疾病的患者中发现了肌肉特异性 microRNAs(miRNAs)的表达失调,称为肌 mirs,尽管在 BMD 中进行了很少的研究。我们分析了 29 名受 BMD 影响的可移动个体队列中一组肌 mirs 的血清表达水平,并根据肌肉活检和 11 名年龄匹配的健康对照者的改变程度进一步进行分类。我们发现我们的 BMD 患者队列中血清 miR-1、miR-133a、miR-133b 和 miR-206 的表达显著上调,支持这些 miRNA 在疾病病理生理学中的作用,我们确定了区分患者和健康对照者的血清截止值水平,证实了循环 miRNA 作为有前途的非侵入性生物标志物的潜力。此外,血清 miR-133b 水平与肌肉活检中的纤维化以及患者的运动表现相关,表明 miR-133b 可能是 BMD 患者的有用预后标志物。总之,我们的数据表明,这些血清肌 mirs 可能代表一种有效的工具,可用于 BMD 患者的分层,为临床试验中监测疾病进展和评估治疗效果提供机会。