An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction
Immune disease-associated non-coding SNPs, which often locate in tissue-specific regulatory elements, are emerging as key factors in gene regulation. Among these elements, long non-coding RNAs (lncRNAs) participate in many cellular processes, and their characteristics make these molecules appealing...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125000873 |
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| author | Ane Olazagoitia-Garmendia Henar Rojas-Márquez Tim Trobisch Cristina Moreno-Castro Ariadne Rodriguez Etxebarria Jon Mentxaka Ajai Tripathi Bibo Yang Itziar Martin Ruiz Juan Anguita J Javier Meana Yiliang Ding Ranjan Dutta Lucas Schirmer Mariana Igoillo-Esteve Izortze Santin Ainara Castellanos-Rubio |
| author_facet | Ane Olazagoitia-Garmendia Henar Rojas-Márquez Tim Trobisch Cristina Moreno-Castro Ariadne Rodriguez Etxebarria Jon Mentxaka Ajai Tripathi Bibo Yang Itziar Martin Ruiz Juan Anguita J Javier Meana Yiliang Ding Ranjan Dutta Lucas Schirmer Mariana Igoillo-Esteve Izortze Santin Ainara Castellanos-Rubio |
| author_sort | Ane Olazagoitia-Garmendia |
| collection | DOAJ |
| description | Immune disease-associated non-coding SNPs, which often locate in tissue-specific regulatory elements, are emerging as key factors in gene regulation. Among these elements, long non-coding RNAs (lncRNAs) participate in many cellular processes, and their characteristics make these molecules appealing therapeutic targets. In this study, we have studied lncRNA LOC339803 in the context of neuronal cells, which is located in autoimmunity-associated region 2p15 and recently described to have a proinflammatory role in intestinal disorders. Using human brain samples and a wide variety of in vitro techniques, we have showed a differential function of this lncRNA in neuronal cells. We have further demonstrated the role of LOC339803 in maintaining hexokinase 2 (HK2) levels and thus mitochondrial integrity, partially explaining the implication of the lncRNA in multiple sclerosis (MS) pathogenesis. Our results show the importance of cell-type-specific studies in the case of regulatory lncRNAs. We present LOC339803 as a candidate for further studies as a mitochondrial dysfunction marker or possible therapeutic target in neurodegeneration. |
| format | Article |
| id | doaj-art-68b4d1ce33bc4338bdf3fd340b78cdae |
| institution | DOAJ |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-68b4d1ce33bc4338bdf3fd340b78cdae2025-08-20T03:18:41ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-06-0136210253310.1016/j.omtn.2025.102533An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunctionAne Olazagoitia-Garmendia0Henar Rojas-Márquez1Tim Trobisch2Cristina Moreno-Castro3Ariadne Rodriguez Etxebarria4Jon Mentxaka5Ajai Tripathi6Bibo Yang7Itziar Martin Ruiz8Juan Anguita9J Javier Meana10Yiliang Ding11Ranjan Dutta12Lucas Schirmer13Mariana Igoillo-Esteve14Izortze Santin15Ainara Castellanos-Rubio16Department of Biochemistry and Molecular Biology, University of Basque Country UPV/EHU, 48940 Leioa, Spain; Biobizkaia Health Research Institute, Cruces-Barakaldo 48903, Spain; Corresponding author: Ane Olazagoitia-Garmendia, Department of Biochemistry and Molecular Biology, University of Basque Country UPV/EHU, Leioa 48940, Spain.Biobizkaia Health Research Institute, Cruces-Barakaldo 48903, Spain; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, 48940 Leioa, SpainDepartment of Neurology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), 1050 Bruxelles, BelgiumDepartment of Biochemistry and Molecular Biology, University of Basque Country UPV/EHU, 48940 Leioa, SpainDepartment of Biochemistry and Molecular Biology, University of Basque Country UPV/EHU, 48940 Leioa, Spain; Biobizkaia Health Research Institute, Cruces-Barakaldo 48903, SpainDepartment of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland OH 44106, USDepartment of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UKCIC bioGUNE-BRTA, 48160 Derio, SpainCIC bioGUNE-BRTA, 48160 Derio, Spain; Ikerbasque, Basque Foundation for Science, 48009 Bilbao, SpainBiobizkaia Health Research Institute, Cruces-Barakaldo 48903, Spain; Department of Pharmacology, University of the Basque Country UPV/EHU, 48940 Leioa, Spain; Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, 28029 Madrid, SpainDepartment of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UKDepartment of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland OH 44106, USDepartment of Neurology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Mannheim Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; Interdisciplinary Center for Neurosciences, Heidelberg University, 69117 Heidelberg, GermanyULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), 1050 Bruxelles, BelgiumDepartment of Biochemistry and Molecular Biology, University of Basque Country UPV/EHU, 48940 Leioa, Spain; Biobizkaia Health Research Institute, Cruces-Barakaldo 48903, Spain; CIBERDEM, 28029 Madrid, SpainBiobizkaia Health Research Institute, Cruces-Barakaldo 48903, Spain; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, 48940 Leioa, Spain; Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain; CIBERDEM, 28029 Madrid, Spain; Corresponding author: Ainara Castellanos-Rubio, Biobizkaia Health Research Institute, Cruces-Barakaldo 48903, SpainImmune disease-associated non-coding SNPs, which often locate in tissue-specific regulatory elements, are emerging as key factors in gene regulation. Among these elements, long non-coding RNAs (lncRNAs) participate in many cellular processes, and their characteristics make these molecules appealing therapeutic targets. In this study, we have studied lncRNA LOC339803 in the context of neuronal cells, which is located in autoimmunity-associated region 2p15 and recently described to have a proinflammatory role in intestinal disorders. Using human brain samples and a wide variety of in vitro techniques, we have showed a differential function of this lncRNA in neuronal cells. We have further demonstrated the role of LOC339803 in maintaining hexokinase 2 (HK2) levels and thus mitochondrial integrity, partially explaining the implication of the lncRNA in multiple sclerosis (MS) pathogenesis. Our results show the importance of cell-type-specific studies in the case of regulatory lncRNAs. We present LOC339803 as a candidate for further studies as a mitochondrial dysfunction marker or possible therapeutic target in neurodegeneration.http://www.sciencedirect.com/science/article/pii/S2162253125000873MT: non-coding RNAslncRNASNPcell-specificityRNA modificationmitochondria |
| spellingShingle | Ane Olazagoitia-Garmendia Henar Rojas-Márquez Tim Trobisch Cristina Moreno-Castro Ariadne Rodriguez Etxebarria Jon Mentxaka Ajai Tripathi Bibo Yang Itziar Martin Ruiz Juan Anguita J Javier Meana Yiliang Ding Ranjan Dutta Lucas Schirmer Mariana Igoillo-Esteve Izortze Santin Ainara Castellanos-Rubio An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction Molecular Therapy: Nucleic Acids MT: non-coding RNAs lncRNA SNP cell-specificity RNA modification mitochondria |
| title | An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction |
| title_full | An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction |
| title_fullStr | An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction |
| title_full_unstemmed | An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction |
| title_short | An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction |
| title_sort | inflammation associated lncrna induces neuronal damage via mitochondrial dysfunction |
| topic | MT: non-coding RNAs lncRNA SNP cell-specificity RNA modification mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125000873 |
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