Dataset Information

Identification of potential therapeutic target genes and miRNAs for primary myelofibrosis with microarray analysis.

ABSTRACT: The aim of the present study was to identify potential therapeutic target genes and miRNAs for primary myelofibrosis (PMF). The dataset GSE53482 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) of peripheral blood (PB) cluster of differentiation (CD)34+ cells from PMF patients (PB-PMF group) and peripheral blood CD34+ cells from healthy individuals (PB-control group) were analyzed using the Linear Models for Microarray Data package in R. The Kyoto Encyclopedia of Genes and Genomes was used for pathway enrichment analysis. MiRNA-gene joint enrichment analysis was performed by ENViz and a miRNAs-gene regulatory network was constructed. A total of 1,182 DEGs (773 upregulated and 109 downregulated) and 48 DEMs (28 upregulated and 20 downregulated) were identified. According to the pathway enrichment analysis, a number of DEGs were enriched in metabolic pathways, including IDH1 and DNMT1. Other DEGs were enriched in the citrate cycle (tricarboxylic acid cycle; IDH1 and IDH3A) and certain DEGs were enriched in pyrimidine metabolism, including CARD8. For downregulated genes, certain DEGs were enriched in the spliceosome, including SF3B1 and CDC40. Furthermore, hsa-miR-127-3p, hsa-miR-140-3p and hsa-miR345 were associated with cell cycle-related biological processes, signal transduction and cell surface receptor signaling pathway. The DEM-DEG regulatory network indicated that hsa-miR-543 regulated 113 genes, including CARD8 and TIFA. The present study identified a number of genes, including IDH1, DNMT1, SF3B1 and CARD8, and miRNAs, including hsa-miR-127-3p and hsa-miR-140-3p, which may be therapeutic targets in the treatment of PMF.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5615205 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Identification of potential therapeutic target genes and miRNAs for primary myelofibrosis with microarray analysis.

Liu Yong Y Wei Bo B Zhang Xuebing X Xu Dehui D Wang Bo B Yin Guochao G Gu Dawer D Li Yuxiang Y Kong Daliang D

Experimental and therapeutic medicine 20170809 4

The aim of the present study was to identify potential therapeutic target genes and miRNAs for primary myelofibrosis (PMF). The dataset GSE53482 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) of peripheral blood (PB) cluster of differentiation (CD)34<sup>+</sup> cells from PMF patients (PB-PMF group) and peripheral blood CD34<sup>+</sup> cells from healthy individuals (PB-control group) were analyzed ...[more]

PMID: 28966666

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Project description:The aim of the present study was to identify genes under the effect of transforming growth factor-β (TGF-β1), high glucose (HG) and glucosamine (GlcN) in MES-13 mesangial cells and elucidate the molecular mechanisms of diabetic nephropathy (DN). The gene expression datasets GSE2557 and GSE2558 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were independently screened using the GEO2R online tool. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape software. The hub genes were identified by the NetworkAnalyzer plugin. Overlapping genes were subjected to molecular docking analysis using SystemsDock. A total of 202 upregulated and 158 downregulated DEGs from the HG-treated groups, 138 upregulated and 103 downregulated DEGs from the GlcN-treated groups, and 81 upregulated and 44 downregulated DEGs from the TGF-β1-treated groups were identified. The majority of the DEGs were independently enriched in 'nucleosome assembly', 'chromatin silencing' and 'xenobiotic glucuronidation'. In addition, KEGG pathways were significantly enriched in 'systemic lupus erythematosus', 'protein processing in endoplasmic reticulum' and 'aldarate metabolism pathway', and 'TNF signaling pathway' intersected in the TGF-β1-treated and HG-treated groups. In total, eight hub genes, Jun, prostaglandin-endoperoxide synthase 2 (Ptgs2), fibronectin 1 (Fn1), cyclin-dependent kinase (Cdk)2, Fos, heat shock protein family A (Hsp70) member 5 (Hspa5), Hsp90b1 and homo sapiens hypoxia upregulated 1 (Hyou1), and three overlapping genes, Ras homolog gene family, member B (RHOB), complement factor H (CFH) and Krüppel-like factor 15 (KLF15), were selected. Valsartan with RHOB, and fosinopril with CFH and KLF15 had preferential binding activity. In conclusion, Jun, Ptgs2, Fn1, Cdk2, Fos, Hspa5, Hsp90b1, Hyou1, RHOB, CFH and KLF15 may be potential therapeutic targets for mesangial cells associated with DN, which may provide insight into DN treatment strategies.

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Dataset Information

Identification of potential therapeutic target genes and miRNAs for primary myelofibrosis with microarray analysis.

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Identification of potential therapeutic target genes and miRNAs for primary myelofibrosis with microarray analysis.

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