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基于生物信息学分析鉴定 IgA 肾病患者外周血单个核细胞中的关键 miRNAs 及其靶基因。

Identification of key miRNAs and their targets in peripheral blood mononuclear cells of IgA nephropathy using bioinformatics analysis.

机构信息

Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical Universtiy, Tiyuchang Road 453#, Hangzhou, Zhejiang, China.

出版信息

Medicine (Baltimore). 2021 Jul 2;100(26):e26495. doi: 10.1097/MD.0000000000026495.

Abstract

BACKGROUND

Currently, renal biopsy is the gold standard for clinical diagnosis and evaluation the degrees of IgA nephropathy. However, renal biopsy is an invasive examination and not suitable for long-term follow-up IgA nephropathy. The activation of peripheral blood mononuclear cells (PBMCs) are related to IgA nephropathy, but the key molecular marker and target of PBMCs for evaluating the progression and prognosis of IgA nephropathy is still unclear.

METHODS

We downloaded gene expression omnibus series 25590 (GSE25590) datasets, of which PBMCs from IgA nephrology (IgAN) and healthy patients, from the gene expression omnibus (GEO) database. Differentially expressed miRNAs (DEMs) between IgAN and healthy patients were identified. The Funrich software was used to predict the differentially expressed genes (DEGs). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyzes of overlapping genes were analyzed at the function level on DAVID 6.8. We used search Tool for the retrieval of interacting genes (STRING) online database constructed the protein-protein interaction (PPI) network. Then we further analyzed the hub genes by Cytoscape software and the hub miRNA by TargetScan.

RESULTS

We identified 418 DEMs from the GSE25590 datasets. The upstream transcription factors SP1 regulates most DEMs. According to the GO and KEGG results, the DEGs were enriched in the MAPK signaling pathway and small GTPase mediated signal transduction. SYN1, SYT4, RBFOX1, KCNC1, VAMP2, FBXO11, ASB9, SYT9, KLHL5, and KRAS were identified as hub genes. Hsa-miR-532-5p, hsa-miR-92a, hsa-miR-328, hsa-miR-137, hsa-miR-153, hsa-miR-9-5p, hsa-miR-140-5p, hsa-miR-217, hsa-miR-155, and hsa-miR-212 were predicted as hub miRNAs.

CONCLUSIONS

The DEMs and DEGs re-analysis provided potential key genes and hub miRNA of PMBCs, which may help to monitor the happening and prognosis of IgAN.

摘要

背景

目前,肾活检是临床诊断和评估 IgA 肾病程度的金标准。然而,肾活检是一种有创检查,不适合长期随访 IgA 肾病。外周血单个核细胞 (PBMC) 的激活与 IgA 肾病有关,但评估 IgA 肾病进展和预后的 PBMC 关键分子标志物和靶点仍不清楚。

方法

我们从基因表达综合 (GEO) 数据库中下载了基因表达谱数据集 25590(GSE25590),其中包括 IgA 肾病 (IgAN) 和健康患者的 PBMC。使用 Funrich 软件预测差异表达基因 (DEGs)。在 DAVID 6.8 上对重叠基因进行基因本体 (GO) 和京都基因与基因组百科全书 (KEGG) 分析,以在功能水平上进行分析。我们使用在线 STRING 数据库构建蛋白质-蛋白质相互作用 (PPI) 网络来搜索相互作用基因 (STRING)。然后我们使用 Cytoscape 软件进一步分析枢纽基因,使用 TargetScan 分析枢纽 miRNA。

结果

我们从 GSE25590 数据集确定了 418 个差异表达 miRNA(DEMs)。上游转录因子 SP1 调节大多数 DEMs。根据 GO 和 KEGG 结果,DEGs 富集在 MAPK 信号通路和小 GTPase 介导的信号转导中。SYN1、SYT4、RBFOX1、KCNC1、VAMP2、FBXO11、ASB9、SYT9、KLHL5 和 KRAS 被鉴定为枢纽基因。hsa-miR-532-5p、hsa-miR-92a、hsa-miR-328、hsa-miR-137、hsa-miR-153、hsa-miR-9-5p、hsa-miR-140-5p、hsa-miR-217、hsa-miR-155 和 hsa-miR-212 被预测为枢纽 miRNA。

结论

对 DEMs 和 DEGs 的重新分析提供了 PMBCs 的潜在关键基因和枢纽 miRNA,这可能有助于监测 IgAN 的发生和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/8257889/00a4cfee795d/medi-100-e26495-g001.jpg

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