Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, and the pathogenesis is influenced by genetic susceptibility. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play essential roles in complex diseases, including acting as competing endogenous RNAs (ceRNAs). However, the functional roles and regulatory mechanisms of lncRNAs acting as ceRNAs in MS are still unclear. In this study, we identified hub lncRNA ceRNAs in MS based on ceRNA mechanisms and annotated their functions. The lncRNA-associated ceRNA network (LACN) was constructed by integrating the expression profiles of lncRNA/mRNA and miRNA in MS and normal samples, and the experimentally validated interactions of lncRNA-miRNA and mRNA-miRNA. We found three hub lncRNA ceRNAs (XIST, OIP5-AS1, and CTB-89H12.4) using the network analysis and obtained 96 lncRNA-mediated competing triplets (LCTs, lncRNA-miRNA-mRNA) with the hub lncRNA ceRNAs, which constituted 3 hub ceRNA modules. The functional analysis identified 12 pathways enriched by the 3 hub lncRNA ceRNAs, of which 6 were confirmed to be related to MS. For example, XIST was enriched in the ‘spliceosome’ and ‘RNA transport’ related to the typing of MS, and CTB-89H12.4 was enriched in the ‘mTOR signaling pathway,’ a potential therapeutic target for MS. We dissected the expression patterns of the 96 LCTs in MS individually. LCT XIST-miR-326-HNRNPA1, for which the expression pattern in MS revealed that XIST and HNRNPA1 were up-regulated and miR-326 was down-regulated, consisted of risk RNAs for MS that were validated by other research. Therefore, XIST-miR-326-HNRNPA1 might play a central role in the pathogenesis of MS. These results will contribute to the discovery of novel biomarkers and the development of new therapeutic methods for MS.

多发性硬化症（MS）是中枢神经系统的一种慢性自身免疫性疾病，其发病机理受遗传易感性的影响。越来越多的证据表明，长的非编码RNA（lncRNA）在复杂疾病中起着至关重要的作用，包括充当竞争性内源性RNA（ceRNA）。然而，尚不清楚在MS中，作为ceRNA的lncRNA的功能作用和调控机制。在这项研究中，我们基于ceRNA机制鉴定了MS中的hub lncRNA ceRNA，并对其功能进行了注释。通过整合lncRNA / mRNA和miRNA在MS和正常样品中的表达谱以及经实验验证的lncRNA-miRNA和mRNA-miRNA的相互作用，构建了与lncRNA相关的ceRNA网络（LACN）。我们发现了三个中枢lncRNA ceRNA（XIST，OIP5-AS1和CTB-89H12.4）通过网络分析获得了96个lncRNA介导的竞争三联体（LCT，lncRNA-miRNA-mRNA）和中枢lncRNA ceRNA，构成了3个中枢ceRNA模块。功能分析确定了由3个枢纽lncRNA ceRNA富集的12条途径，其中6条被证实与MS相关。例如，XIST富含与MS类型相关的“剪接体”和“ RNA转运”，而CTB-89H12.4富含“ mTOR信号传导途径”，这是MS的潜在治疗靶标。我们分别剖析了96个LCT在MS中的表达模式。LCT XIST -miR-326- HNRNPA1，其在MS中的表达模式显示XISTHNRNPA1和HNRNPA1被下调，miR-326被下调，由MS的风险RNA组成，该RNA已被其他研究证实。因此，XIST -miR-326- HNRNPA1可能在MS的发病机理中起核心作用。这些结果将有助于发现新型生物标志物和开发新的MS治疗方法。