Dataset Information

MicroRNAs and regulated interaction networks reveal differences between adult and pediatric acute myeloid leukemia.

ABSTRACT: OBJECTIVES:The purpose of this study was to identify featured microRNAs and their regulated network between adult and pediatric acute myeloid leukemia (AML) and find potential utility as biomarkers for diagnosis and treatment of pediatric AML. METHODS:We downloaded the microRNA expression dataset GSE35320 from Gene Expression Omnibus database and selected expression chips from bone marrow of 71 pediatric AML samples and 6 adulthood AML samples. Differentially expressed microRNAs were identified by Wilcox test. The target genes of these microRNAs were predicted using an integrative method and their functional enrichment analysis was performed using DAVID. Finally, STRING database and Cytoscape software was used to construct and analyze the interaction network. RESULTS:A total of 7 differentially expressed microRNAs were identified and the remarkably up-regulated and down-regulated microRNAs were miR-16 and miR-142-5p which included 323 and 22 predicted target genes, respectively. The target genes of 7 microRNAs were most associated with regulation of cell cycle, p53 signaling pathway, Wnt signaling pathway and neurotrophin signaling pathway. The interaction network of miR-16 target genes was constructed among 354 high confidence interaction pairs. The core genes of the network, such as TP53, BCL2, VEGFA, had a role in prognosis of children with AML. CONCLUSIONS:The featured microRNAs and their target genes are significant in the occurrence and development of pediatric AML, which is likely to be important for the identification of therapeutic targets and biomarkers for these patients.

SUBMITTER: Liu J

PROVIDER: S-EPMC6965806 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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MicroRNAs and regulated interaction networks reveal differences between adult and pediatric acute myeloid leukemia.

Liu Jing J Zhou Lei L Fu Xiaomin X Xu Chen C Huang Sai S Li Yan Y Gao Honghao H Guan Wei W Yang Lan L Lv Na N

International journal of clinical and experimental pathology 20171001 10

<h4>Objectives</h4>The purpose of this study was to identify featured microRNAs and their regulated network between adult and pediatric acute myeloid leukemia (AML) and find potential utility as biomarkers for diagnosis and treatment of pediatric AML.<h4>Methods</h4>We downloaded the microRNA expression dataset GSE35320 from Gene Expression Omnibus database and selected expression chips from bone marrow of 71 pediatric AML samples and 6 adulthood AML samples. Differentially expressed microRNAs w ...[more]

PMID: 31966399

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Project description:Background: Associated with poor prognosis, FMS-like tyrosine kinase 3 (FLT3) mutation appeared frequently in acute myeloid leukemia (AML). Herein, we aimed to identify the key genes and miRNAs involved in adult AML with FLT3 mutation and find possible therapeutic targets for improving treatment. Materials: Gene and miRNA expression data and survival profiles were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. EdgeR of R platform was applied to identify the differentially expressed genes and miRNAs (DEGs, DE-miRNAs). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape and DAVID. And protein-protein interaction network, miRNA-mRNA regulatory network and clustering modules analyses were performed by STRING database and Cytoscape software. Results: Survival analysis showed FLT3 mutation led to adverse outcome in AML. 24 DE-miRNAs (6 upregulated, 18 downregulated) and 250 DEGs (54 upregulated, 196 downregulated) were identified. Five miRNAs had prognostic value and the results matched their expression levels (miR-1-3p, miR-10a-3p, miR-10a-5p, miR-133a-3p and miR-99b-5p). GO analysis showed DEGs were enriched in skeletal system development, blood vessel development, cartilage development, tissue morphogenesis, cartilage morphogenesis, cell morphogenesis involved in differentiation, response to growth factor, cell-substrate adhesion and so on. The KEGG analysis showed DEGs were enriched in PI3K-Akt signaling pathway, ECM-receptor interaction and focal adhesion. Seven genes (LAMC1, COL3A1, APOB, COL1A2, APP, SPP1 and FSTL1) were simultaneously identified by hub gene analysis and module analysis. SLC14A1, ARHGAP5 and PIK3CA, the target genes of miR-10a-3p, resulted in poor prognosis. Conclusion: Our study successfully identified molecular markers, processes and pathways affected by FLT3 mutation in AML. Furthermore, miR-10a-3p, a novel oncogene, might involve in the development of FLT3 mutation adult AML by targeting SLC14A1, ARHGAP5 and PIK3CA.

Dataset Information

MicroRNAs and regulated interaction networks reveal differences between adult and pediatric acute myeloid leukemia.

Publications

MicroRNAs and regulated interaction networks reveal differences between adult and pediatric acute myeloid leukemia.

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