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Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes.

ABSTRACT: The Metnase fusion gene consists of a SET histone methyltransferase domain and a transposase domain from Mariner transposase. This transposable element is involved in chromosome decatenation, enhances DNA repair, promotes foreign DNA integration, and assists topoisomerase II function. This study investigates the role of Metnase in colon cancer homeostasis and maintenance of the stemness phenotype in colon cancer stem cells (CSCs). Silencing of Metnase was performed in human cancer cell lines before and after treatment with cisplatin, and in colon CSCs. Subsequent changes in the expression of genes involved in repair mechanisms, DNA synthesis, topoisomerase II function, and metastasis as well stemness transcription factors were studied with RT-qPCR experiments. Cellular viability and apoptosis were evaluated by flow cytometry. The results suggest that Metnase influences the expression of many genes involved in the above processes. Furthermore, Metnase levels appear to impact upon expression of NANOG, OCT3/4, and SOX2. Suppression of Metnase also led to an increase in apoptosis. Therefore, Metnase may possess an important role in DNA repair, topoisomerase II function, and the maintenance of stemness during colon cancer development.

SUBMITTER: Apostolou P

PROVIDER: S-EPMC4198141 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes.

Apostolou Panagiotis P Toloudi Maria M Kourtidou Eleni E Mimikakou Georgia G Vlachou Ioanna I Chatziioannou Marina M Kipourou Vasiliki V Papasotiriou Ioannis I

PloS one 20141015 10

The Metnase fusion gene consists of a SET histone methyltransferase domain and a transposase domain from Mariner transposase. This transposable element is involved in chromosome decatenation, enhances DNA repair, promotes foreign DNA integration, and assists topoisomerase II function. This study investigates the role of Metnase in colon cancer homeostasis and maintenance of the stemness phenotype in colon cancer stem cells (CSCs). Silencing of Metnase was performed in human cancer cell lines bef ...[more]

PMID: 25333365

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Project description:Background Colon cancer (CC) is one of the tumors with high morbidity and mortality in the world, and has a trend of younger generation. The molecular level of CC has not been fully elaborated. The purpose of this study is to screen and identify important genes with poor prognosis and their mechanisms at different levels. Methods GSE74602 and GSE10972 gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. There were 58 normal tissues and 58 CC tissues. Differentially expressed genes (DEGs) were screened out by using the GEO2R tool and Venn diagram. Then, the DAVID online database was used to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Six hub genes with the highest correlation were screened out after the modular analysis of the protein-protein interaction (PPI) network by using Cytoscape’s MCODE plug-in. Finally, the overall survival of key hub genes and potential pathways were verified in GEPIA and UALCAN database. Results A total of 78 up-regulated DEGs were enriched in the mitotic nuclear division, cell division, cell proliferation, anaphase-promoting complex-dependent catabolic process and G2/M transition of the mitotic cell cycle. In total, 130 down-regulated DEGs were enriched in muscle contraction, bicarbonate transport, cellular response to zinc ion, negative regulation of growth, negative regulation of leukocyte apoptotic process and one-carbon metabolic process. CDK1, CCNB1, CDC20, AURKA, CCNA2 and TOP2A were the top six hub genes, mainly enriched in cell cycle pathways. Among them, CCNB1, CDK1, CDC20, CCNA2 were enriched in the G2/M phase. GEPIA and UALCAN database confirmed that CCNA2 and CCNB1 had a significant relationship with the poor prognosis of CC patients. Meanwhile, there was a positive correlation between the two. Conclusions Screening out genes with abnormal expression in CC help understand the initiation and progression of CC at the molecular level and explore candidate biomarkers for diagnosis, treatment and prognosis.

Dataset Information

Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes.

Publications

Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes.

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