Department of Neurology, The second Affiliated hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang Province, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Nangang District, Harbin, Heilongjiang Province, China.
Mult Scler Relat Disord. 2020 Jun;41:102044. doi: 10.1016/j.msard.2020.102044. Epub 2020 Mar 5.
It has been widely acknowledged that abnormal expression of microRNAs (miRNAs) may lead to the occurrence and development of MS through regulating target genes. Currently, only few studies have comprehensively evaluated the function and relationship between MS-related miRNAs and their target genes.
Differentially expressed miRNAs in MS patients' serum and plasma were selected by reviewing numerous literatures manually. Then, thousands of target genes were screened by several online databases, of which 899 MS-related genes were further identified. Gene ontology, protein-protein interaction and KEGG pathway analysis were used to determine high-risk pathways and MS risk genes. Transcriptomic datasets from GEO was analyzed to evaluate these risk genes.
28 MS-related miRNAs were extracted. MiR-30e, miR-93, miR-155 were identified as the most crucial miRNAs through targeting hub genes: PIK3CA, PIK3R1, PIK3R2 and MAPK8. Seven immune pathways were screened out according to KEGG pathway analysis. Six transcriptomic datasets were used to evaluate results, and PIK3CA was differentially expressed in MS patients compared with healthy donors.
According to our research, MS-related miRNAs and their target genes of MS were identified and comprehensively evaluated. This work may provide a new insight for discovering pathogenesis and possible biomarkers of MS in future studies.
已有研究证实，微小 RNA（miRNA）异常表达可能通过调控靶基因导致多发性硬化（MS）的发生发展。目前，仅有少数研究综合评估了 MS 相关 miRNA 及其靶基因的功能和关系。
通过手动查阅大量文献，选择 MS 患者血清和血浆中差异表达的 miRNA。然后，通过多个在线数据库筛选出数千个靶基因，其中进一步鉴定出 899 个 MS 相关基因。通过基因本体论、蛋白质-蛋白质相互作用和京都基因与基因组百科全书（KEGG）通路分析确定高风险通路和 MS 风险基因。利用 GEO 转录组数据集评估这些风险基因。
提取出 28 个 MS 相关 miRNA。通过靶向关键基因 PIK3CA、PIK3R1、PIK3R2 和 MAPK8，鉴定出 miR-30e、miR-93 和 miR-155 为最关键的 miRNA。根据 KEGG 通路分析筛选出 7 条免疫通路。使用 6 个转录组数据集评估结果，发现 MS 患者与健康供者相比 PIK3CA 表达存在差异。
根据我们的研究，鉴定出 MS 相关 miRNA 及其靶基因，并对其进行了综合评估。这项工作可能为未来研究中发现 MS 的发病机制和潜在生物标志物提供新的思路。
