An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction

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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
MT: non-coding RNAs
lncRNA
SNP
cell-specificity
RNA modification
mitochondria
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253125000873
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Summary: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.
ISSN:2162-2531

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