PMID- 33507382 OWN - NLM STAT- MEDLINE DCOM- 20210225 LR - 20210225 IS - 1617-4623 (Electronic) IS - 1617-4623 (Linking) VI - 296 IP - 2 DP - 2021 Mar TI - Identification of hub lncRNA ceRNAs in multiple sclerosis based on ceRNA mechanisms. PG - 423-435 LID - 10.1007/s00438-020-01750-1 [doi] AB - 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. FAU - Ding, Yanjun AU - Ding Y AUID- ORCID: 0000-0003-3980-7701 AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. AD - Department of Microbiology, WU Lien-Teh Institute, Harbin Medical University, Harbin, 150086, China. FAU - Li, Taotao AU - Li T AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. FAU - Yan, Xinwei AU - Yan X AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. FAU - Cui, Mintian AU - Cui M AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. FAU - Wang, Chao AU - Wang C AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. FAU - Wang, Situo AU - Wang S AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. FAU - Zhang, Fengmin AU - Zhang F AD - Department of Microbiology, WU Lien-Teh Institute, Harbin Medical University, Harbin, 150086, China. fengminzhang@ems.hrbmu.edu.cn. FAU - Zhang, Ruijie AU - Zhang R AD - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. zhangrj@ems.hrbmu.edu.cn. LA - eng GR - LH2019C043/Natural Science Foundation of Heilongjiang Province/ PT - Journal Article DEP - 20210128 PL - Germany TA - Mol Genet Genomics JT - Molecular genetics and genomics : MGG JID - 101093320 RN - 0 (Biomarkers, Tumor) RN - 0 (Heterogeneous Nuclear Ribonucleoprotein A1) RN - 0 (MIRN326 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) RN - 0 (XIST non-coding RNA) RN - 0 (hnRNPA1 protein, human) SB - IM MH - Biomarkers, Tumor/genetics MH - Databases, Genetic MH - Gene Expression Profiling MH - Gene Expression Regulation MH - Gene Regulatory Networks MH - Genetic Predisposition to Disease MH - Heterogeneous Nuclear Ribonucleoprotein A1/*genetics MH - Humans MH - MicroRNAs/*genetics MH - Molecular Sequence Annotation MH - Multiple Sclerosis/*genetics MH - RNA, Long Noncoding/*genetics MH - RNA, Messenger/genetics OTO - NOTNLM OT - CeRNAs OT - LncRNAs OT - MS OT - ceRNA network OT - lncRNA-mediated competing triplets EDAT- 2021/01/29 06:00 MHDA- 2021/02/26 06:00 CRDT- 2021/01/28 12:14 PHST- 2020/06/26 00:00 [received] PHST- 2020/12/08 00:00 [accepted] PHST- 2021/01/29 06:00 [pubmed] PHST- 2021/02/26 06:00 [medline] PHST- 2021/01/28 12:14 [entrez] AID - 10.1007/s00438-020-01750-1 [pii] AID - 10.1007/s00438-020-01750-1 [doi] PST - ppublish SO - Mol Genet Genomics. 2021 Mar;296(2):423-435. doi: 10.1007/s00438-020-01750-1. Epub 2021 Jan 28.