Circular RNA expression in ALS is progressively deregulated and tissue-dependent
Abstract Background 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 skele...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12864-025-11725-4 |
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| author | Leticia Moreno-García Laura Moreno-Martínez Miriam de la Torre Sofía Macías-Redondo Alberto García-Redondo Rosario Osta Janne Markus Toivonen Ana Cristina Calvo |
| author_facet | Leticia Moreno-García Laura Moreno-Martínez Miriam de la Torre Sofía Macías-Redondo Alberto García-Redondo Rosario Osta Janne Markus Toivonen Ana Cristina Calvo |
| author_sort | Leticia Moreno-García |
| collection | DOAJ |
| description | Abstract Background 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). Results 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. Conclusions 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. Graphical Abstract |
| format | Article |
| id | doaj-art-43cc35ed8a8a400f89d41135a3ba2a07 |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj-art-43cc35ed8a8a400f89d41135a3ba2a072025-08-20T03:45:47ZengBMCBMC Genomics1471-21642025-07-0126112110.1186/s12864-025-11725-4Circular RNA expression in ALS is progressively deregulated and tissue-dependentLeticia Moreno-García0Laura Moreno-Martínez1Miriam de la Torre2Sofía Macías-Redondo3Alberto García-Redondo4Rosario Osta5Janne Markus Toivonen6Ana Cristina Calvo7Laboratory 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)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)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)Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA)Genetic Diagnosis and Research Lab, Neurology Department, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12)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)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)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)Abstract Background 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). Results 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. Conclusions 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. Graphical Abstracthttps://doi.org/10.1186/s12864-025-11725-4Non-coding RNACircular RNAAmyotrophic lateral sclerosisSOD1G93A miceNeurodegenerationCentral nervous system |
| spellingShingle | Leticia Moreno-García Laura Moreno-Martínez Miriam de la Torre Sofía Macías-Redondo Alberto García-Redondo Rosario Osta Janne Markus Toivonen Ana Cristina Calvo Circular RNA expression in ALS is progressively deregulated and tissue-dependent BMC Genomics Non-coding RNA Circular RNA Amyotrophic lateral sclerosis SOD1G93A mice Neurodegeneration Central nervous system |
| title | Circular RNA expression in ALS is progressively deregulated and tissue-dependent |
| title_full | Circular RNA expression in ALS is progressively deregulated and tissue-dependent |
| title_fullStr | Circular RNA expression in ALS is progressively deregulated and tissue-dependent |
| title_full_unstemmed | Circular RNA expression in ALS is progressively deregulated and tissue-dependent |
| title_short | Circular RNA expression in ALS is progressively deregulated and tissue-dependent |
| title_sort | circular rna expression in als is progressively deregulated and tissue dependent |
| topic | Non-coding RNA Circular RNA Amyotrophic lateral sclerosis SOD1G93A mice Neurodegeneration Central nervous system |
| url | https://doi.org/10.1186/s12864-025-11725-4 |
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