Identification of hub lncRNA ceRNAs in multiple sclerosis based on ceRNA mechanisms

Abstract

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.

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Acknowledgements

This work was supported by the Natural Science Foundation of Heilongjiang Province (Grant No. LH2019C043). We would like to express our gratitude to EditSprings (https://www.editsprings.com/) for the expert linguistic services provided.

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YD: data curation, formal analysis, methodology, writing—original draft. TL: investigation, resources. XY: investigation, resources. MC: validation, visualization. CW: validation, visualization. SW: software. FZ: project administration, supervision, writing—review and editing. RZ: conceptualization, funding acquisition, project administration, supervision, writing—review and editing.

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Correspondence to Fengmin Zhang or Ruijie Zhang.

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Ding, Y., Li, T., Yan, X. et al. Identification of hub lncRNA ceRNAs in multiple sclerosis based on ceRNA mechanisms. Mol Genet Genomics 296, 423–435 (2021). https://doi.org/10.1007/s00438-020-01750-1

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Keywords

  • MS
  • LncRNAs
  • CeRNAs
  • ceRNA network
  • lncRNA-mediated competing triplets