Dataset Information

Uncoordinated expression of DNA methylation-related enzymes in human cancer.

ABSTRACT: In addition to the important roles played by 5-methylcytosine (5mC), emerging evidence suggests that 5mC derivatives, such as 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), also exhibit regulatory functions in physiological and pathological processes. Four cytosine modifications (5mC, 5hmC, 5fC and 5caC) are produced and erased by a cyclic enzymatic cascade mediated by DNA methyltransferases (DNMTs), ten-eleven translocation (TET) family enzymes and thymine DNA glycosylase (TDG). Stable maintenance of the DNA methylation profile is important for normal cell homeostasis, but its underlying mechanisms are largely unknown.The expression levels of 7 DNA methylation-related enzymes from normal mouse tissues were assessed using quantitative real-time RT-PCR (qRT-PCR). The gene expression data and related information of human normal tissues and tumor tissues were obtained from the Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA), respectively.We observed significant positive correlations among the expression levels of DNA methylation-related enzymes in various mice and human normal tissues. By contrast, we found significantly decreased correlations in various tumor tissues compared with their corresponding normal tissues. Furthermore, we also found that alterations in these correlations are associated with several clinicopathological characteristics of cancer patients.These observations suggest that uncoordinated expression of DNA methylation-related enzymes is another epigenetic hallmark of cancer. Our work provides important insights into an additional regulatory layer of the DNA methylation maintenance machinery.

SUBMITTER: Liu J

PROVIDER: S-EPMC5727647 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Uncoordinated expression of DNA methylation-related enzymes in human cancer.

Liu Jiao J Cui Xiuliang X Jiang Jinhua J Cao Dan D He Yufei Y Wang Hongyang H

Epigenetics & chromatin 20171212 1

<h4>Background</h4>In addition to the important roles played by 5-methylcytosine (5mC), emerging evidence suggests that 5mC derivatives, such as 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), also exhibit regulatory functions in physiological and pathological processes. Four cytosine modifications (5mC, 5hmC, 5fC and 5caC) are produced and erased by a cyclic enzymatic cascade mediated by DNA methyltransferases (DNMTs), ten-eleven translocation (TET) family ...[more]

PMID: 29233176

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Project description:Osteoarthritis (OA) is chronic arthritis characterized by articular cartilage degradation. However, a comprehensive regulatory network for OA-related microRNAs and DNA methylation modifications has yet to be established. Thus, we aimed to identify epigenetic changes in microRNAs and DNA methylation and establish the regulatory network between miRNAs and DNA methylation. The mRNA, miRNA, and DNA methylation expression profiles of healthy or osteoarthritis articular cartilage samples were downloaded from Gene Expression Omnibus (GEO) database, including GSE169077, GSE175961, and GSE162484. The differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially methylated genes (DMGs) were analyzed by the online tool GEO2R. DAVID and STRING databases were applied for functional enrichment analysis and protein-protein interaction (PPI) network. Potential therapeutic compounds for the treatment of OA were identified by Connectivity map (CMap) analysis. A total of 1424 up-regulated DEGs, 1558 down-regulated DEGs, 5 DEMs with high expression, 6 DEMs with low expression, 1436 hypermethylated genes, and 455 hypomethylated genes were selected. A total of 136 up-regulated and 65 downregulated genes were identified by overlapping DEGs and DEMs predicted target genes which were enriched in apoptosis and circadian rhythm. A total of 39 hypomethylated and 117 hypermethylated genes were obtained by overlapping DEGs and DMGs, which were associated with ECM receptor interactions and cellular metabolic processes, cell connectivity, and transcription. Moreover, The PPI network showed COL5A1, COL6A1, LAMA4, T3GAL6A, and TP53 were the most connective proteins. After overlapping of DEGs, DMGs and DEMs predicted targeted genes, 4 up-regulated genes and 11 down-regulated genes were enriched in the Axon guidance pathway. The top ten genes ranked by PPI network connectivity degree in the up-regulated and downregulated overlapping genes of DEGs and DMGs were further analyzed by the CMap database, and nine chemicals were predicted as potential drugs for the treatment of OA. In conclusion, TP53, COL5A1, COL6A1, LAMA4, and ST3GAL6 may play important roles in OA genesis and development.

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Uncoordinated expression of DNA methylation-related enzymes in human cancer.

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Uncoordinated expression of DNA methylation-related enzymes in human cancer.

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