| 孟德尔随机化联合Meta分析miRNA 在溃疡性结肠炎中的关系及潜在机制 |
| 投稿时间：2024-08-22 修订日期：2024-08-27 点此下载全文 |
| 引用本文：陈旭永,杨小红,吴海东,王柳,丹，苗新普.孟德尔随机化联合Meta分析miRNA 在溃疡性结肠炎中的关系及潜在机制[J].医学研究杂志,2025,54(2):88-95 |
| DOI：
10.11969/j.issn.1673-548X.2025.02.015 |
| 摘要点击次数: 374 |
| 全文下载次数: 102 |
|
| 基金项目:国家自然科学基金资助项目(82160104) |
|
| 中文摘要:目的 通过孟德尔随机化(Mendelian randomization, MR)联合Meta分析(MR-Meta分析)并结合生物信息学分析挖掘,旨在鉴定microRNA(miRNA)与溃疡性结肠炎(ulcerative colitis, UC)之间的因果关系,并分析其潜在的生物学功能和通路,以寻找新的生物学标志物和潜在的治疗靶点。方法 利用miRNA暴露数据和多个UC结局数据集,通过MR-Meta分析鉴定miRNA与UC间的因果关系。随后利用基因表达数据库提取UC的微阵列数据进行差异分析,对MR-Meta-miRNA进行差异表达检测,并将检测的候选miRNA差异靶基因进行机器学习算法筛选出关键基因。然后通过免疫细胞浸润、单基因富集分析(gene set enrichment analysis, GSEA)关键基因的功能和通路,并构建ceRNA调控网络。结果 通过MR-Meta分析鉴定出9个miRNA与UC风险显著相关。通过GES48959芯片数据分析显示hsa-miR-196b-5p在UC组织中显著低表达,随后将hsa-miR-196b-5p靶向的差异基因通过2种机器学习算法得到了关键基因MAP3K1。经GSEA和免疫浸润分析显示,MAP3K1是调节免疫炎症的关键基因。ceRNA调控网络表明,lncRNA/hsa-miR-196b-5p/MAP3K1具有调节UC病变的潜力。结论miRNA与UC存在因果关系,其中hsa-miR-196b-5p与UC风险密切相关,hsa-miR-196b-5p/MAP3K1通路可能作为调控UC免疫炎症的分子机制影响疾病的发生和进展,并为今后探索UC的有效诊断和治疗提供了新的思路。 |
| 中文关键词:溃疡性结肠炎 孟德尔随机化 microRNA Meta分析 MAP3K1 |
| |
| Relationship and Potential Mechanisms between MiRNA and Ulcerative Colitis from Meta-analysis of Mendelian Randomization. |
|
|
| Abstract:Objective Mendelian randomization (MR) combined with Meta-analysis (MR-Meta analysis) and bioinformatics mining were used to identify the causal relationship between microRNA (miRNA) and ulcerative colitis (UC). The potential biological functions and pathways were analyzed to search for new biomarkers and potential therapeutic targets. Methods MiRNA exposure data and multiple UC outcome data sets were used to identify the causal relationship between miRNA and UC by MR-meta analysis. Then, the microarray data of UC was extracted by gene expression database for differential analysis, the differential expression of MR-Meta-miRNAs was detected, and the differential target genes of the detected candidate miRNA were screened by machine learning algorithm for key genes. Then, the function and pathway of key genes were analyzed by immune cell infiltration and single gene enrichment analysis (GSEA), and the ceRNA regulatory network was constructed. Results Nine miRNA were identified by MR-Meta analysis and were significantly associated with UC risk. The GES48959 chip data analysis showed that the hsa-miR-196b-5p was significantly low-expressed in UC tissues, the differential genes targeted by hsa-miR-196b-5p were then used to obtain the key gene MAP3K1 by two machine learning algorithms. GSEA and immune-infiltration analysis showed that MAP3K1 was a key gene in regulating immune inflammation. The ceRNA regulatory network indicates that lncRNA/hsa-miR-196b-5p/MAP3K1had the potential to regulate UC lesions. Conclusion There is a causal relationship between miRNA and UC, among which hsa-miR-196b-5p is closely related to the risk of UC. The hsa-miR-196b-5p/MAP3K1 pathway may affect the occurrence and progression of diseases as a molecular mechanism regulating UC immune inflammation, and provide a new idea for exploring the effective diagnosis and treatment of UC in the future. |
| keywords:Ulcerative colitis Mendelian randomization MicroRNA Meta-analysis MAP3K1 |
| 查看全文 查看/发表评论 下载PDF阅读器 |
|
|
|
