Sabaie Hani, Khorami Rouz Sharareh, Kouchakali Ghazal, Heydarzadeh Samaneh, Asadi Mohammad Reza, Sharifi-Bonab Mirmohsen, Hussen Bashdar Mahmud, Taheri Mohammad, Ayatollahi Seyed Abdulmajid, Rezazadeh Maryam
Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
School of Life Sciences, Manipal University, Dubai, United Arab Emirates.
Front Genet. 2022 Oct 17;13:1011350. doi: 10.3389/fgene.2022.1011350. eCollection 2022.
Slow-burning inflammation at the lesion rim is connected to the expansion of chronic multiple sclerosis (MS) lesions. However, the underlying processes causing expansion are not clearly realized. In this context, the current study used a bioinformatics approach to identify the expression profiles and related lncRNA-associated ceRNA regulatory axes in the periplaque region in MS patients. Expression data (GSE52139) from periplaque regions in the secondary progressive MS spinal cord and controls were downloaded from the Gene Expression Omnibus database (GEO), which has details on mRNAs and lncRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also found using the DIANA-LncBase, miRTarBase, and HMDD databases. The Pearson correlation coefficient was used to determine whether there were any positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Finally, lncRNA-associated ceRNA axes were created based on co-expression and connections between DElncRNA, miRNA, and DEmRNA. We used the Enrichr tool to enrich the biological process, molecular function, and pathways for DEmRNAs and DElncRNAs. A network of DEmRNAs' protein-protein interactions was developed, and the top five hub genes were found using Cytoscape and STRING. The current study indicates that 15 DEmRNAs, including , , , , and , are connected to the MS ceRNA network. Additionally, four DElncRNAs (such as , , and ) that regulated the aforementioned mRNAs by sponging 14 MS-related miRNAs (e.g., , , , , , , , , ) were found. In addition, the analysis of pathway enrichment revealed that DEmRNAs were enriched in the pathways for the "MAPK signaling pathway", "Kaposi sarcoma-associated herpesvirus infection", "Human immunodeficiency virus one infection", "Lipid and atherosclerosis", and "Amphetamine addiction". Even though the function of these ceRNA axes needs to be investigated further, this study provides research targets for studying ceRNA-mediated molecular mechanisms related to periplaque demyelination in MS.
病灶边缘的慢性炎症与慢性多发性硬化症（MS）病灶的扩展有关。然而，导致病灶扩展的潜在过程尚未完全明确。在此背景下，本研究采用生物信息学方法，以确定MS患者斑块周围区域的表达谱以及相关的长链非编码RNA（lncRNA）相关的竞争性内源性RNA（ceRNA）调控轴。从基因表达综合数据库（GEO）下载了继发进展型MS脊髓斑块周围区域和对照的表达数据（GSE52139），该数据库包含mRNA和lncRNA的详细信息。使用R软件的limma包，找出差异表达的lncRNA（DElncRNA）和mRNA（DEmRNA）。还利用DIANA-LncBase、miRTarBase和HMDD数据库发现RNA相互作用。使用Pearson相关系数来确定ceRNA网络中DEmRNA和DElncRNA之间是否存在正相关。最后，基于DElncRNA、miRNA和DEmRNA之间的共表达和连接创建lncRNA相关的ceRNA轴。我们使用Enrichr工具对DEmRNA和DElncRNA的生物学过程、分子功能和通路进行富集分析。构建了DEmRNA的蛋白质-蛋白质相互作用网络，并使用Cytoscape和STRING找出前五个枢纽基因。本研究表明，包括[具体基因1]、[具体基因2]、[具体基因3]、[具体基因4]和[具体基因5]在内的15个DEmRNA与MS的ceRNA网络相关。此外，发现了4个DElncRNA（如[具体lncRNA1]、[具体lncRNA2]和[具体lncRNA3]），它们通过吸附14种与MS相关的miRNA（例如[具体miRNA1]、[具体miRNA2]、[具体miRNA3]、[具体miRNA4]、[具体miRNA5]、[具体miRNA6]、[具体miRNA7]、[具体miRNA8]）来调控上述mRNA。此外，通路富集分析显示，DEmRNA在“MAPK信号通路”、“卡波西肉瘤相关疱疹病毒感染”、“人类免疫缺陷病毒1型感染”、“脂质与动脉粥样硬化”和“苯丙胺成瘾”等通路中富集。尽管这些ceRNA轴的功能需要进一步研究，但本研究为研究MS中与斑块周围脱髓鞘相关的ceRNA介导的分子机制提供了研究靶点。
