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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Hauptverfasser: Olazagoitia-Garmendia, Ane (VerfasserIn) , Rojas-Márquez, Henar (VerfasserIn) , Trobisch, Tim (VerfasserIn) , Moreno-Castro, Cristina (VerfasserIn) , Rodriguez Etxebarria, Ariadne (VerfasserIn) , Mentxaka, Jon (VerfasserIn) , Tripathi, Ajai (VerfasserIn) , Yang, Bibo (VerfasserIn) , Martin Ruiz, Itziar (VerfasserIn) , Anguita, Juan (VerfasserIn) , Meana, J. Javier (VerfasserIn) , Ding, Yiliang (VerfasserIn) , Dutta, Ranjan (VerfasserIn) , Schirmer, Lucas (VerfasserIn) , Igoillo-Esteve, Mariana (VerfasserIn) , Santin, Izortze (VerfasserIn) , Castellanos-Rubio, Ainara (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 10 June 2025
In: Molecular therapy. Nucleic Acids
Year: 2025, Jahrgang: 36, Heft: 2, Pages: 1-15
ISSN:2162-2531
DOI:10.1016/j.omtn.2025.102533
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.omtn.2025.102533
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2162253125000873
Volltext
Verfasserangaben: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, and Ainara Castellanos-Rubio

MARC

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520 |a 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. 
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