Department of Biotechnology, Jozef Stefan Institute, Jamova 39, Ljubljana, Slovenia.
Institute of Clinical Neurophysiology, Division of Neurology, University Medical Centre Ljubljana, Zaloška cesta 7, Ljubljana, Slovenia.
Sci Rep. 2018 Apr 4;8(1):5609. doi: 10.1038/s41598-018-23139-2.
Amyotrophic lateral sclerosis is a late-onset disorder primarily affecting motor neurons and leading to progressive and lethal skeletal muscle atrophy. Small RNAs, including microRNAs (miRNAs), can serve as important regulators of gene expression and can act both globally and in a tissue-/cell-type-specific manner. In muscle, miRNAs called myomiRs govern important processes and are deregulated in various disorders. Several myomiRs have shown promise for therapeutic use in cellular and animal models of ALS; however, the exact miRNA species differentially expressed in muscle tissue of ALS patients remain unknown. Following small RNA-Seq, we compared the expression of small RNAs in muscle tissue of ALS patients and healthy age-matched controls. The identified snoRNAs, mtRNAs and other small RNAs provide possible molecular links between insulin signaling and ALS. Furthermore, the identified miRNAs are predicted to target proteins that are involved in both normal processes and various muscle disorders and indicate muscle tissue is undergoing active reinnervation/compensatory attempts thus providing targets for further research and therapy development in ALS.
肌萎缩侧索硬化症是一种迟发性疾病，主要影响运动神经元，导致进行性和致命的骨骼肌萎缩。小 RNA，包括 microRNAs（miRNAs），可以作为基因表达的重要调节剂，既可以全局作用，也可以组织/细胞类型特异性作用。在肌肉中，称为肌源性 miRNAs 的 miRNAs 控制着重要的过程，并在各种疾病中失调。一些肌源性 miRNAs 在 ALS 的细胞和动物模型中显示出治疗应用的潜力；然而，ALS 患者肌肉组织中差异表达的确切 miRNA 种类仍不清楚。在进行了小 RNA-Seq 之后，我们比较了 ALS 患者和年龄匹配的健康对照组肌肉组织中小 RNA 的表达。鉴定出的 snoRNAs、mtRNAs 和其他小 RNA 为胰岛素信号与 ALS 之间提供了可能的分子联系。此外，鉴定出的 miRNAs 预测靶向参与正常过程和各种肌肉疾病的蛋白质，表明肌肉组织正在进行主动再神经支配/代偿尝试，从而为 ALS 的进一步研究和治疗开发提供了目标。
