Moreno-García Leticia, Moreno-Martínez Laura, de la Torre Miriam, Macías-Redondo Sofía, García-Redondo Alberto, Osta Rosario, Toivonen Janne Markus, Calvo Ana Cristina
Laboratory of Genetics and Biochemistry (LAGENBIO), Department of Anatomy, Embryology and Animal Genetics, Veterinary Faculty, University of Zaragoza, Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), Agroalimentary Institute of Aragon (IA2), Zaragoza, Spain.
Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza, Spain.
BMC Genomics. 2025 Jul 1;26(1):576. doi: 10.1186/s12864-025-11725-4.
There is increasing evidence on the role of circular RNAs (circRNAs) in neuronal and muscular processes. Accordingly, their dysregulation is associated with neurodegenerative diseases and myopathies. We investigated circRNA expression in the central nervous system (CNS) and skeletal muscle, the two main tissues affected in amyotrophic lateral sclerosis (ALS).
Based on circRNA sequencing analysis in spinal cord from ALS mice (SOD1G93A) followed by a literature search, 30 circRNAs potentially involved in ALS were tested. All selected circRNAs were downregulated in the SOD1G93A spinal cord, whereas only half of these were quantifiable and were generally upregulated in quadriceps muscle of SOD1G93A mice. Such tissue-dependent expression pattern was observed in both sexes and circRNA abundance in the spinal cord was higher than in the muscle, both in wild type and in SOD1G93A mice. Finally, we assessed the 18 circRNAs with the largest expression differences and the highest degree of interspecies conservation in brain samples from sporadic ALS (sALS) patients and healthy controls. Similar to the mouse model, circRNA levels tended to decrease in the CNS of sALS patients.
Expression of circRNAs may be systematically altered in the two tissues most affected by ALS in a progressive and opposed manner. Although more detailed studies are warranted, circRNAs are potentially related to ALS etiopathogenesis and could possibly serve as future biomarkers, therapeutic targets, or customized therapeutic tools to modulate the pathology.
越来越多的证据表明环状RNA（circRNA）在神经元和肌肉过程中发挥作用。因此，它们的失调与神经退行性疾病和肌病有关。我们研究了环状RNA在中枢神经系统（CNS）和骨骼肌中的表达，这是肌萎缩侧索硬化症（ALS）中受影响的两个主要组织。
基于对ALS小鼠（SOD1G93A）脊髓的环状RNA测序分析并随后进行文献检索，测试了30种可能与ALS相关的环状RNA。所有选定的环状RNA在SOD1G93A脊髓中均下调，而其中只有一半是可量化的，并且在SOD1G93A小鼠的股四头肌中通常上调。在野生型和SOD1G93A小鼠中，两性均观察到这种组织依赖性表达模式，并且脊髓中的环状RNA丰度高于肌肉中的。最后，我们评估了散发性ALS（sALS）患者和健康对照的脑样本中表达差异最大且种间保守程度最高的18种环状RNA。与小鼠模型相似，sALS患者中枢神经系统中的环状RNA水平倾向于降低。
环状RNA的表达可能在ALS影响最严重的两个组织中以渐进且相反的方式发生系统性改变。尽管需要更详细的研究，但环状RNA可能与ALS的发病机制有关，并有可能作为未来的生物标志物、治疗靶点或定制的治疗工具来调节病理过程。
