Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy.
Cell Mol Life Sci. 2020 Nov;77(21):4299-4313. doi: 10.1007/s00018-020-03537-4. Epub 2020 Apr 29.
Noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs, are key regulators of gene expression at the post-transcriptional level and represent promising therapeutic targets and biomarkers for several human diseases, including Duchenne and Becker muscular dystrophies (DMD/BMD). A role for ncRNAs in the pathogenesis of muscular dystrophies has been suggested, even if it is still incompletely understood. Here, we discuss current progress leading towards the clinical utility of ncRNAs for DMD/BMD. Long and short noncoding RNAs are differentially expressed in DMD/BMD and have a mechanism of action via targeting mRNAs. A subset of muscle-enriched miRNAs, the so-called myomiRs (miR-1, miR-133, and miR-206), are increased in the serum of patients with DMD and in dystrophin-defective animal models. Interestingly, myomiRs might be used as biomarkers, given that their levels can be corrected after dystrophin restoration in dystrophic mice. Remarkably, further evidence demonstrates that ncRNAs also play a role in dystrophin expression; thus, their modulations might represent a potential therapeutic strategy with the aim of upregulating the dystrophin protein in combination with other oligonucleotides/gene therapy approaches.
非编码 RNA（ncRNA），如 microRNA 和长非编码 RNA，是基因表达在转录后水平的关键调节剂，代表了几种人类疾病（包括杜氏肌营养不良症和贝克肌营养不良症）有前途的治疗靶点和生物标志物。ncRNA 在肌肉疾病发病机制中的作用已被提出，尽管其机制仍不完全清楚。在这里，我们讨论了将 ncRNA 用于 DMD/BMD 的临床应用的最新进展。长链和短链非编码 RNA 在 DMD/BMD 中表达不同，通过靶向 mRNAs 发挥作用。一组称为肌源性 miRNAs（miR-1、miR-133 和 miR-206）的富含肌肉的 miRNAs 在 DMD 患者的血清中和肌营养不良蛋白缺陷的动物模型中增加。有趣的是，miRNAs 可以作为生物标志物，因为它们的水平可以在肌营养不良蛋白缺陷小鼠中恢复肌营养不良蛋白后得到纠正。值得注意的是，进一步的证据表明，ncRNA 也在肌营养不良蛋白表达中发挥作用；因此，它们的调节可能代表一种潜在的治疗策略，旨在与其他寡核苷酸/基因治疗方法相结合上调肌营养不良蛋白。
