Siegismund Christine S, Rohde Maria, Kühl Uwe, Escher Felicitas, Schultheiss Heinz Peter, Lassner Dirk
Institute for Cardiac Diagnostics and Therapy (IKDT), 12203 Berlin, Germany.
Institute for Cardiac Diagnostics and Therapy (IKDT), 12203 Berlin, Germany; Department of Cardiology, Campus Virchow, Charité - University Hospital Berlin, 13353 Berlin, Germany.
Genomics Proteomics Bioinformatics. 2016 Aug;14(4):224-34. doi: 10.1016/j.gpb.2016.04.005. Epub 2016 Jul 28.
MicroRNAs (miRNAs) can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples (tissue, serum, peripheral blood mononuclear cells or other body fluids) differ significantly even in the same patient and therefore have their own specificity for the presented condition. Complex profiles of deregulated miRNAs are of high interest, whereas the importance of non-expressed miRNAs was ignored. Since miRNAs regulate gene expression rather negatively, absent miRNAs could indicate genes with unaltered expression that therefore are normally expressed in specific compartments or under specific disease situations. For the first time, non-detectable miRNAs in different tissues and body fluids from patients with different diseases (cardiomyopathies, Alzheimer's disease, bladder cancer, and ocular cancer) were analyzed and compared in this study. miRNA expression data were generated by microarray or TaqMan PCR-based platforms. Lists of absent miRNAs of primarily cardiac patients (myocardium, blood cells, and serum) were clustered and analyzed for potentially involved pathways using two prediction platforms, i.e., miRNA enrichment analysis and annotation tool (miEAA) and DIANA miRPath. Extensive search in biomedical publication databases for the relevance of non-expressed miRNAs in predicted pathways revealed no evidence for their involvement in heart-related pathways as indicated by software tools, confirming proposed approach.
微小RNA(miRNA)存在于多种组织和体液中,其特定特征可用于疾病诊断或临床病程预测。即使是同一患者,生物样本(组织、血清、外周血单核细胞或其他体液)中的miRNA谱也存在显著差异,因此对所呈现的病情具有自身的特异性。失调miRNA的复杂谱备受关注,而未表达miRNA的重要性却被忽视。由于miRNA对基因表达主要起负调控作用,未检测到的miRNA可能表明基因表达未改变,这些基因通常在特定的细胞区室或特定疾病情况下表达。本研究首次对不同疾病(心肌病、阿尔茨海默病、膀胱癌和眼癌)患者的不同组织和体液中未检测到的miRNA进行了分析和比较。miRNA表达数据通过微阵列或基于TaqMan PCR的平台生成。使用两个预测平台,即miRNA富集分析和注释工具(miEAA)以及DIANA miRPath,对主要心脏病患者(心肌、血细胞和血清)未检测到的miRNA列表进行聚类,并分析潜在涉及的途径。在生物医学出版物数据库中广泛搜索未表达miRNA在预测途径中的相关性,结果表明没有证据表明它们参与了软件工具所显示的与心脏相关的途径,从而证实了所提出的方法。