MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers
MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in different cellular functions that have emerged as key regulators of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). ALS is a fatal disease that lacks of not only effective treatments, but also presents delay...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000877 |
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| author | Eva P. Cuevas Enrique Madruga Ignacio Valenzuela-Martínez David Ramírez Carmen Gil Siranjeevi Nagaraj Angeles Martin-Requero Ana Martinez |
| author_facet | Eva P. Cuevas Enrique Madruga Ignacio Valenzuela-Martínez David Ramírez Carmen Gil Siranjeevi Nagaraj Angeles Martin-Requero Ana Martinez |
| author_sort | Eva P. Cuevas |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in different cellular functions that have emerged as key regulators of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). ALS is a fatal disease that lacks of not only effective treatments, but also presents delays in its diagnosis, since reliable clinical biomarkers are unavailable. In recent years, advancements in high-throughput sequencing strategies have led to the identification of novel ALS biomarkers, facilitating earlier diagnosis and assessment of treatment efficacy. Since immortalized lymphocytes obtained from peripheral blood are a suitable model to study pathological features of ALS, we employed these samples with the aim of characterize the dysregulated miRNAs in ALS patients. Next-generation sequencing (NGS) was utilized in order to analyze the expression profiles of miRNAs in immortalized lymphocytes from healthy controls, sporadic ALS (sALS), and familial ALS with mutations in superoxide dismutase 1 (SOD1-ALS). The screening analysis of the NGS data identified a set of dysregulated miRNAs, of which nine candidates were selected for qRT-PCR validation, identifying for the first time the possible importance of hsa-miR-6821-5p as a potential ALS biomarker. Furthermore, the up-regulated miRNAs identified are predicted to have direct or indirect interactions with genes closely related to ALS, such as SIGMAR1, HNRNPA1 and TARDBP. Additionally, by Metascape enrichment analysis, we found the VEGFA/VEGFR2 signaling pathway, previously implicated in neuroprotective effects in ALS, as a candidate pathway for further analyses. |
| format | Article |
| id | doaj-art-e3d0ae26f5c445e897b8716793770e43 |
| institution | OA Journals |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-e3d0ae26f5c445e897b8716793770e432025-08-20T02:09:31ZengElsevierNeurobiology of Disease1095-953X2025-05-0120810687110.1016/j.nbd.2025.106871MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkersEva P. Cuevas0Enrique Madruga1Ignacio Valenzuela-Martínez2David Ramírez3Carmen Gil4Siranjeevi Nagaraj5Angeles Martin-Requero6Ana Martinez7Centro de Investigaciones Biológicas “Margarita Salas”-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, SpainCentro de Investigaciones Biológicas “Margarita Salas”-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, SpainDepartamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, ChileDepartamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, ChileCentro de Investigaciones Biológicas “Margarita Salas”-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, SpainAlzheimer and other tauopathies research group, ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 route de Lennik, B-1070 Brussels, BelgiumCentro de Investigaciones Biológicas “Margarita Salas”-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, SpainCentro de Investigaciones Biológicas “Margarita Salas”-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; Corresponding author.MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in different cellular functions that have emerged as key regulators of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). ALS is a fatal disease that lacks of not only effective treatments, but also presents delays in its diagnosis, since reliable clinical biomarkers are unavailable. In recent years, advancements in high-throughput sequencing strategies have led to the identification of novel ALS biomarkers, facilitating earlier diagnosis and assessment of treatment efficacy. Since immortalized lymphocytes obtained from peripheral blood are a suitable model to study pathological features of ALS, we employed these samples with the aim of characterize the dysregulated miRNAs in ALS patients. Next-generation sequencing (NGS) was utilized in order to analyze the expression profiles of miRNAs in immortalized lymphocytes from healthy controls, sporadic ALS (sALS), and familial ALS with mutations in superoxide dismutase 1 (SOD1-ALS). The screening analysis of the NGS data identified a set of dysregulated miRNAs, of which nine candidates were selected for qRT-PCR validation, identifying for the first time the possible importance of hsa-miR-6821-5p as a potential ALS biomarker. Furthermore, the up-regulated miRNAs identified are predicted to have direct or indirect interactions with genes closely related to ALS, such as SIGMAR1, HNRNPA1 and TARDBP. Additionally, by Metascape enrichment analysis, we found the VEGFA/VEGFR2 signaling pathway, previously implicated in neuroprotective effects in ALS, as a candidate pathway for further analyses.http://www.sciencedirect.com/science/article/pii/S0969996125000877miRNAALSBiomarkerLymphoblasts |
| spellingShingle | Eva P. Cuevas Enrique Madruga Ignacio Valenzuela-Martínez David Ramírez Carmen Gil Siranjeevi Nagaraj Angeles Martin-Requero Ana Martinez MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers Neurobiology of Disease miRNA ALS Biomarker Lymphoblasts |
| title | MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers |
| title_full | MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers |
| title_fullStr | MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers |
| title_full_unstemmed | MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers |
| title_short | MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers |
| title_sort | microrna signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers |
| topic | miRNA ALS Biomarker Lymphoblasts |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000877 |
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