NSUN5 is Upregulated and Positively Correlated with Translation in Human Cancers: A Bioinformatics-based Study
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Abstract The role of RNA m 5 C (5-methylcytosine) and RNA m 5 C methyltransferases (RCMTs, including NSUN1, NSUN2, NSUN3, NSUN4, NSUN5, NSUN6, NSUN7 and TRDMT1) in human cancers remains largely unknown. In this study, GEPIA2 was used to compare the expression of RCMTs in human cancers and that in associated normal tissues, and to analyze the prognosis value of NSUN5 expression. UALCAN was used to compare the methylation level of NSUN5 promoter in human cancers and that in associated normal tissues. LinkedOmics was used perform BPs (biological processes), CCs (cellular components), MFs (molecular functions) and KEGG pathways analyses of NSUN5-correlated genes in each cancer one by one. We found that six RCMTs (NSUN1-NSUN5 and TRDMT1), especially NSUN5, were generally upregulated in human cancers, that the hypomethylation of NSUN5 promoter may be responsible for its upregulation, and that overexpressed NSUN5 predicted poorer prognosis and was positively correlated with translation in human cancers. The function of NSUN5 in human cancers and its mechanism need to be validated by biological experiments.Keywords:
KEGG
The aim of the study was to conduct a functional analysis of sex-specific age-related changes in DNA methylation.Materials and Methods.The study used a GSE87571 methylation dataset obtained from the blood DNA of 729 individuals aged 14 to 94 using the Illumina Infinium HumanMethylation450K BeadChip (USA).Gene ontology analysis was performed for 3 groups of genes (females, males, and duplicates) using the PANTHER database.The DAVID platform was used to perform KEGG metabolic pathway analysis.Results.The studies revealed unique for males and females changes in methylation of CpG sites, associated with certain metabolic processes.It was demonstrated that most of the CpG sites, for which methylation changes with age were revealed in both sexes, are associated with the genes responsible for the development and functioning of the nervous system.In males, unique age-related methylation changes affect CpG sites associated with changes in the immune system and lipid metabolism.In females, most CpGs are associated with changes involved in transcription and translation processes.Analysis of biological functions by KEGG revealed that a unique process associated with age-related changes in methylation of the glutamatergic system is typical for males.In females, unique biological processes with age-related changes include genes responsible for the development of diabetes and genes associated with cAMP signaling cascades (KEGG:04024). Conclusion.Our studies reveal fundamental features of sex-dependent changes in methylation of CpG sites with variance increasing, which may indicate differences in age-related changes.
KEGG
CpG site
Differentially methylated regions
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This current study explored the effects of fine particulate matter (PM2.5) on deoxyribonucleic acid methylation in human bronchial epithelial cells. Human bronchial epithelial cells were exposed to PM2.5 for 24 h after which, deoxyribonucleic acid samples were extracted, and the differences between methylation sites were detected using methylation chips. Subsequent gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the differential methylation sites. Functional epigenetic modules analysis of the overall differential methylation site interactions was also conducted. A total of 127 differential methylation sites in 89 genes were screened in the PM2.5 10 μg/ml group, of which 55 sites demonstrated increased methylation, with methylation levels decreasing in a further 72 sites. Following an exposure of 50 μg/ml PM2.5, a total of 238 differentially methylated sites were screened in 168 genes, of which methylation levels increased in 127 sites, and decreased in 111. KEGG analysis showed that the top 10 enrichment pathways predominantly involve hepatocellular carcinoma pathways and endometrial cancer pathways, whereas functional epigenetic modules analysis screened eight genes (A2M, IL23A, TPIP6, IL27, MYD88, ILE2B, NLRC4, TNF) with the most interactions. Our results indicate that exposure to PM2.5 for 24 h in human bronchial epithelial cells induces marked changes in deoxyribonucleic acid methylation of multiple genes involved in apoptosis and carcinogenesis pathways, these findings can provide a new direction for further study of PM2.5 carcinogenic biomarkers.
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GSTP1
Biological pathway
Methylated DNA immunoprecipitation
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Objective:The aim of this study is to detect differentially methylated genes to allergic rhinitis (AR) based on methylation chip, and to analyze the relationship between DNA methylation and AR.Method:Illumina methylation chip were made by normal inferior turbinate mucous tissue obtained from patients(n=19) and healthy individuals(n=11). Detection of differential the sites of methylated genes, Gene Ontology enrichment, KEGG pathway enrichment database and literature search were used to analysis.Result:There were 94 aberrant methylation sites in patients with AR, including 51 hypermethylation sites (e.g. ST7,LCE2D,ATRIP genes) and 43 hypomethylation sites (e.g. PIK3CG, TLR6, IL-4 genes). The results of Gene Ontology enrichment and KEGG pathway enrichment indicates the DNA methylation has relative trend with AR, and DNA methylation of ST7, LCE2D, PIK3CG genes may be associated with AR, but the results of GO analysis and KEGG analysis were statistically significant. Moreover, literature search prompts that DNA methylation of TLR6 gene and IL-4 gene may be associated with AR.Conclusion:Varying degrees of methylated genes from inferior turbinate mucous tissue based on high-flux methylation chip hint gene methylation is an important cause of AR. The relationship between them needs further verification.
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The ability to target methylation to specific genomic sites would further the study of DNA methylation's biological role and potentially offer a tool for silencing gene expression and for treating diseases involving abnormal hypomethylation. The end-to-end fusion of DNA methyltransferases to zinc fingers has been shown to bias methylation to desired regions. However, the strategy is inherently limited because the methyltransferase domain remains active regardless of whether the zinc finger domain is bound at its cognate site and can methylate non-target sites. We demonstrate an alternative strategy in which fragments of a DNA methyltransferase, compromised in their ability to methylate DNA, are fused to two zinc fingers designed to bind 9 bp sites flanking a methylation target site. Using the naturally heterodimeric DNA methyltransferase M.EcoHK31I, which methylates the inner cytosine of 5′-YGGCCR-3′, we demonstrate that this strategy can yield a methyltransferase capable of significant levels of methylation at the target site with undetectable levels of methylation at non-target sites in Escherichia coli. However, some non-target methylation could be detected at higher expression levels of the zinc finger methyltransferase indicating that further improvements will be necessary to attain the desired exclusive target specificity.
DNA methyltransferase
RNA-Directed DNA Methylation
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Abstract Vegetarians have a lower intake of vitamin B
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DNA methylation is essential for mammalian development, X-chromosome inactivation, and imprinting yet aberrant methylation patterns are one of the most common features of transformed cells. One of the proposed causes for these defects in the methylation machinery is overexpression of one or more of the three known catalytically active DNA methyltransferases (DNMTs) 1, 3a and 3b, yet there are clearly examples in which overexpression is minimal or non-existent but global methylation anomalies persist. An alternative mechanism which could give rise to global methylation errors is the improper expression of one or more of the DNMTs during the cell cycle. To begin to study the latter possibility we examined the expression of the mRNAs for DNMT1, 3a and 3b during the cell cycle of normal and transformed cells. We found that DNMT1 and 3b levels were significantly downregulated in G(0)/G(1)while DNMT3a mRNA levels were less sensitive to cell cycle alterations and were maintained at a slightly higher level in tumor lines compared to normal cell strains. Enzymatic activity assays revealed a similar decrease in the overall methylation capacity of the cells during G(0)/G(1)arrest and again revealed that a tumor cell line maintained a higher methylation capacity during arrest than a normal cell strain. These results reveal a new level of control exerted over the cellular DNA methylation machinery, the loss of which provides an alternative mechanism for the genesis of the aberrant methylation patterns observed in tumor cells.
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DNA methyltransferase
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Previous studies have shown that DNA methylation plays a significant role in myelodysplastic syndrome (MDS). In addition to hypermethylation, aberrant hypomethylation can result in the transcriptional activation of oncogenes in cancer, including MDS. Therefore, drugs targeting DNA hypomethylation are needed for the treatment of MDS. This study aimed to investigate whether As2S2 promoted hypomethylation by increasing DNA methyltransferases (DNMTs) expression in MDS. Ten bone marrow samples from MDS patients and 3 healthy donors were obtained for the examination of the DNA methylation with a Human Methylation 850K BeadChip. The mRNA expressions for the DNMTs in the ten MDS patients and 3 controls were compared by Q-PCR. Then, the MDS cell line SKM-1 was treated with As2S2. After 2 days of treatment, Human Methylation 850K BeadChip was applied to analyze the changes of gene methylation status in the cells. Q-PCR and Western blot were taken to test the changes of mRNA and protein expressions for DNMTs in SKM-1 cells after treatment. Five hundred ninety-two abnormally hypomethylated genes were found in MDS patients compared to those in controls by Human Methylation 850K. The mRNA expressions of DNMTs (DNMT1, DNMT3a and DNMT3b) in MDS patients were significantly lower than those in healthy individuals. The IC50 value of As2S2 for SKM-1 cells was 4.97 μmol/L.Treatment with As2S2 at 2 μmoL/L resulted in significant alterations in the methylation levels at 1718 sites in SKM-1 cells compared to those in the controls. Hypermethylation was observed in 1625 sites (94.58%), corresponding to 975 genes, compared to those in the controls. Finally, the expression levels of DNMTs (DNMT1, DNMT3a, and DNMT3b) significantly increased in SKM-1 cells treated with As2S2 at 2 μmoL/L and 4 μmoL/L. These data show a potential clinical application of As2S2 as an innovative hypermethylation agent in MDS.
DNMT3B
DNMT1
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Abstract Factors such as chemical fertilizers used in recent years, incorrect irrigation techniques, changing climatic conditions increase the accumulation of cadmium (Cd) heavy metal in the soil. In study, it was aimed to determine the expression levels of stress-related genes in the plant and the methylation levels for the first time by Real-Time PCR-based quantitative DNA methylation analysis (qAMP) after Cd stress applied at different concentrations to bread wheat ( Triticum aestivum L .), which is an important agricultural product. The development of wheat plants exposed to Cd stress at 0,100, 250, 500 µM doses was achieved and DNA and RNA isolations were performed from these plants. While the gene expression analyze was performed with the cDNAs produced by designing primers specific to the selected gene regions, the DNA methylation ratio were determined by applying the restriction enzyme-based qAMP technique. The obtained results were compared with gene expression analysis. Gene expression levels and DNA methylation percentages of UGT-3, LTP-4 and PIP-1 genes were determined under CdCl 2 stress. The percentage of methylation in the UGT-3, LTP-4 and PIP-1 genes was determined at the highest concentration of 250 µM in both the shoot and root. The expression level of the UGT-3 gene gave the highest rate at 250 µM dose in the shoot, while the overexpression of the LTP-4 gene was observed at 250 µM concentration in the root. The changes in methylation rates of UGT-3, LTP-4 and PIP-1 genes were investigated for the first time with qAMP in plants. A significant correlation was observed between the expression levels of genes and their methylation status.
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To assess the role of DNA cytosine methylation in the expression of the O-6-methylguanine DNA methyltransferase (MGMT) gene, the methylation status of selected CpG-containing dinucleotides in and surrounding the coding regions of the gene were examined and correlated with steady state expression of MGMT mRNA in 13 human cell lines. Additionally, tumor cells which exhibited very high levels of MGMT expression were chronically exposed to 5-azacytidine to assess the effects of changes in gene methylation on MGMT expression. Results of these studies demonstrate that the degree of methylation of multiple MGMT gene regions correlates with gene expression, but in a direct rather than an inverse fashion, and that 5-azacytidine-induced demethylation of the MGMT gene correlates with a significant reduction, rather than induction, of MGMT steady-state mRNA expression. These results suggest a unique, potentially alterable methylation-related regulatory mechanism for the MGMT gene.
CpG site
DNA methyltransferase
RNA-Directed DNA Methylation
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