Olazagoitia-Garmendia Ane, Rojas-Márquez Henar, Trobisch Tim, Moreno-Castro Cristina, Rodriguez Etxebarria Ariadne, Mentxaka Jon, Tripathi Ajai, Yang Bibo, Martin Ruiz Itziar, Anguita Juan, Meana J Javier, Ding Yiliang, Dutta Ranjan, Schirmer Lucas, Igoillo-Esteve Mariana, Santin Izortze, Castellanos-Rubio Ainara
Department of Biochemistry and Molecular Biology, University of Basque Country UPV/EHU, 48940 Leioa, Spain.
Biobizkaia Health Research Institute, Cruces-Barakaldo 48903, Spain.
Mol Ther Nucleic Acids. 2025 Apr 2;36(2):102533. doi: 10.1016/j.omtn.2025.102533. eCollection 2025 Jun 10.
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 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 techniques, we have showed a differential function of this lncRNA in neuronal cells. We have further demonstrated the role of 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 as a candidate for further studies as a mitochondrial dysfunction marker or possible therapeutic target in neurodegeneration.
与免疫疾病相关的非编码单核苷酸多态性（SNP）通常位于组织特异性调控元件中，正逐渐成为基因调控的关键因素。在这些元件中，长链非编码RNA（lncRNA）参与许多细胞过程，其特性使这些分子成为有吸引力的治疗靶点。在本研究中，我们在神经元细胞的背景下研究了位于自身免疫相关区域2p15的lncRNA，该lncRNA最近被描述在肠道疾病中具有促炎作用。通过使用人脑样本和多种技术，我们展示了这种lncRNA在神经元细胞中的差异功能。我们进一步证明了其在维持己糖激酶2（HK2）水平从而维持线粒体完整性方面的作用，部分解释了该lncRNA在多发性硬化症（MS）发病机制中的作用。我们的结果表明，在调控lncRNA的情况下，细胞类型特异性研究非常重要。我们提出将其作为进一步研究的候选对象，作为神经退行性疾病中线粒体功能障碍的标志物或可能的治疗靶点。
