Cheng Liu, Yonggui Wu
Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China (mainland).
Med Sci Monit. 2017 Jan 4;23:38-45. doi: 10.12659/msm.899385.
BACKGROUND Uremia involves a series of clinical manifestations and is a common syndrome that occurs in nearly all end-stage kidney diseases. However, the exact genetic and/or molecular mechanisms that underlie uremia remain poorly understood. MATERIAL AND METHODS In this case-control study, we analyzed whole-genome microarray of 75 uremia patients and 20 healthy controls to investigate changes in gene expression and cellular mechanisms relevant to uremia. Gene co-expression network analysis was performed to construct co-expression networks using differentially expressed genes (DEGs) in uremia. We then determined hub models of co-expressed gene networks by MCODE, and we used miRNA enrichment analysis to detect key miRNAs in each hub module. RESULTS We found nine co-expressed hub modules implicated in uremia. These modules were enriched in specific biological functions, including "proteolysis", "membrane-enclosed lumen", and "apoptosis". Finally, miRNA enrichment analysis to detect key miRNAs in each hub module found 15 miRNAs that were specifically targeted to uremia-related hub modules. Of these, miRNA-21-3p and miRNA-210-3p have been identified in other studies as being important for uremia. CONCLUSIONS In summary, our study connected biological functions, genes, and miRNAs that underpin the network modules that can be used to elucidate the molecular mechanisms involved in uremia.
尿毒症涉及一系列临床表现,是几乎所有终末期肾病中都会出现的常见综合征。然而,尿毒症确切的遗传和/或分子机制仍知之甚少。
在这项病例对照研究中,我们分析了75例尿毒症患者和20名健康对照者的全基因组微阵列,以研究与尿毒症相关的基因表达变化和细胞机制。利用尿毒症中的差异表达基因(DEG)进行基因共表达网络分析以构建共表达网络。然后我们通过MCODE确定共表达基因网络的枢纽模型,并使用miRNA富集分析来检测每个枢纽模块中的关键miRNA。
我们发现了9个与尿毒症相关的共表达枢纽模块。这些模块富含特定的生物学功能,包括“蛋白水解”、“膜封闭腔”和“凋亡”。最后,通过miRNA富集分析来检测每个枢纽模块中的关键miRNA,发现了15个特异性靶向尿毒症相关枢纽模块的miRNA。其中,miRNA-21-3p和miRNA-210-3p在其他研究中已被确定对尿毒症很重要。
总之,我们的研究将支撑网络模块的生物学功能、基因和miRNA联系起来,这些网络模块可用于阐明尿毒症所涉及的分子机制。