■炎症性肠病(IBD),包括溃疡性结肠炎(UC)和克罗恩病(CD),是慢性的,胃肠道复发性炎症。microRNA(miRNA)-mRNA调控网络在IBD的发生和发展中起着关键作用。尽管个别研究为IBD中miRNA的机制提供了有价值的见解,由于人口多样性的限制,它们的范围往往有限,样本量,测序平台可变性,批处理效果,和潜在的研究人员偏见。我们的研究旨在构建完整的miRNA-mRNA调控网络,并确定IBD发病机制中关键miRNA的细胞来源和功能。
■为了最大限度地减少个体研究的潜在偏差,我们对PubMed和PMC数据库中已发表的科学文献采用了基于文本挖掘的方法,以鉴定与IBD及其亚型相关的miRNA和mRNA.我们通过整合来自DIANA的预测和实验验证结果,构建了miRNA-mRNA调控网络。Targetscan,PicTar,米兰达,miRDB,和miRTarBase(所有这些都是miRNA靶标注释的数据库)。通过对其靶mRNA的基因富集分析来确定miRNA的功能。此外,我们使用两个大规模单细胞RNA测序数据集来鉴定miRNA的细胞来源及其表达水平与临床状态的关联,CD和UC的分子和功能交替。
■我们的分析使用文本挖掘方法系统地总结了IBD相关基因。我们构建了三个针对IBD的miRNA-mRNA调控网络,CD,和UC。通过对两个大规模scRNA-seq数据集的交叉分析,我们确定了鉴定的miRNA的细胞来源。尽管来自不同的细胞类型,hsa-miR-142、hsa-miR-145和hsa-miR-146a在CD和UC中是常见的。值得注意的是,hsa-miR-145在CD和UC中均被鉴定为肌成纤维细胞特异性。此外,我们发现,在CD和UC患者的肌成纤维细胞中,较高的组织修复和增强的糖脂代谢与hsa-miR-145相关.
■这种综合方法揭示了CD和UC中常见和不同的miRNA-mRNA调控网络,鉴定的细胞特异性miRNA表达(特别是肌成纤维细胞中的hsa-miR-145),并将miRNA表达与IBD的功能改变相关联。这些发现不仅增强了我们对IBD发病机制的理解,而且为管理IBD的临床实践提供了有希望的诊断生物标志物和治疗靶标。
UNASSIGNED: Inflammatory Bowel Diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn\'s Disease (CD), are chronic, recurrent inflammatory conditions of the gastrointestinal tract. The microRNA (miRNA) -mRNA regulatory network is pivotal in the initiation and progression of IBDs. Although individual studies provide valuable insights into miRNA mechanisms in IBDs, they often have limited scope due to constraints in population diversity, sample size, sequencing platform variability, batch effects, and potential researcher bias. Our study aimed to construct comprehensive miRNA-mRNA regulatory networks and determine the cellular sources and functions of key miRNAs in IBD pathogenesis.
UNASSIGNED: To minimize potential bias from individual studies, we utilized a text mining-based approach on published scientific literature from PubMed and PMC databases to identify miRNAs and mRNAs associated with IBDs and their subtypes. We constructed miRNA-mRNA regulatory networks by integrating both predicted and experimentally validated results from DIANA, Targetscan, PicTar, Miranda, miRDB, and miRTarBase (all of which are databases for miRNA target annotation). The functions of miRNAs were determined through gene enrichment analysis of their target mRNAs. Additionally, we used two large-scale single-cell RNA sequencing datasets to identify the cellular sources of miRNAs and the association of their expression levels with clinical status, molecular and functional alternation in CD and UC.
UNASSIGNED: Our analysis systematically summarized IBD-related genes using text-mining methodologies. We constructed three comprehensive miRNA-mRNA regulatory networks specific to IBD, CD, and UC. Through cross-analysis with two large-scale scRNA-seq datasets, we determined the cellular sources of the identified miRNAs. Despite originating from different cell types, hsa-miR-142, hsa-miR-145, and hsa-miR-146a were common to both CD and UC. Notably, hsa-miR-145 was identified as myofibroblast-specific in both CD and UC. Furthermore, we found that higher tissue repair and enhanced glucose and lipid metabolism were associated with hsa-miR-145 in myofibroblasts in both CD and UC contexts.
UNASSIGNED: This comprehensive approach revealed common and distinct miRNA-mRNA regulatory networks in CD and UC, identified cell-specific miRNA expressions (notably hsa-miR-145 in myofibroblasts), and linked miRNA expression to functional alterations in IBD. These findings not only enhance our understanding of IBD pathogenesis but also offer promising diagnostic biomarkers and therapeutic targets for clinical practice in managing IBDs.