scholarly journals Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6039
Author(s):  
Bo Xu ◽  
Hao Wang ◽  
Li Tan
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Embryonic Development ◽  
Cellular Differentiation ◽  
Epigenetic Modification ◽  
Current Understanding ◽  
Future Perspectives ◽  
Cancer Hallmarks ◽  
The Past

DNA methylation (5-methylcytosine, 5mC) was once viewed as a stable epigenetic modification until Rao and colleagues identified Ten-eleven translocation 1 (TET1) as the first 5mC dioxygenase in 2009. TET family genes (including TET1, TET2, and TET3) encode proteins that can catalyze 5mC oxidation and consequently modulate DNA methylation, not only regulating embryonic development and cellular differentiation, but also playing critical roles in various physiological and pathophysiological processes. Soon after the discovery of TET family 5mC dioxygenases, aberrant 5mC oxidation and dysregulation of TET family genes have been reported in breast cancer as well as other malignancies. The impacts of aberrant 5mC oxidation and dysregulated TET family genes on the different aspects (so-called cancer hallmarks) of breast cancer have also been extensively investigated in the past decade. In this review, we summarize current understanding of the causes and consequences of aberrant 5mC oxidation in the pathogenesis of breast cancer. The challenges and future perspectives of this field are also discussed.

scholarly journals Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

2009 ◽  
Vol 11 ◽  
Author(s):  
Stephen G. Grant ◽  
Melissa A. Melan ◽  
Jean J. Latimer ◽  
Paula A. Witt-Enderby
Keyword(s):  
Breast Cancer ◽  
Cellular Differentiation ◽  
Cellular Proliferation ◽  
Future Perspectives ◽  
Cellular Mechanisms ◽  
Cellular Toxicity ◽  
Signalling Cascades ◽  
Free Radical Formation ◽  
Second Messenger Pathways ◽  
Potential Use

Recent studies have suggested that the pineal hormone melatonin may protect against breast cancer, and the mechanisms underlying its actions are becoming clearer. Melatonin works through receptors and distinct second messenger pathways to reduce cellular proliferation and to induce cellular differentiation. In addition, independently of receptors melatonin can modulate oestrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity. The fact that melatonin works through a myriad of signalling cascades that are protective to cells makes this hormone a good candidate for use in the clinic for the prevention and/or treatment of cancer. This review summarises cellular mechanisms governing the action of melatonin and then considers the potential use of melatonin in breast cancer prevention and treatment, with an emphasis on improving clinical outcomes.

Programming and Inheritance of Parental DNA Methylomes in Vertebrates

Physiology ◽  
2015 ◽  
Vol 30 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Weimin Ci ◽  
Jiang Liu
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Epigenetic Modification ◽  
Early Embryogenesis ◽  
Recent Advances

5-Methylcytosine (5mC) is a major epigenetic modification in animals. The programming and inheritance of parental DNA methylomes ensures the compatibility for totipotency and embryonic development. In vertebrates, the DNA methylomes of sperm and oocyte are significantly different. During early embryogenesis, the paternal and maternal methylomes will reset to the same state. Herein, we focus on recent advances in how offspring obtain the DNA methylation information from parents in vertebrates.

scholarly journals Epigenetics: Pharmacology and Modification Mechanisms Involved in Cardiac, Hepatic and Renal Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 260-266
Author(s):  
Sagar. S. Waghmare ◽  
O.G. Bhusnure ◽  
M. R. Mali ◽  
S.T. Mule
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Epigenetic Modification ◽  
Hepatic Disease ◽  
Human Diseases ◽  
Future Perspective ◽  
The Past

For a long time scientists have tried to describe disorders are due to genetic as well as environmental factors. In the past few years, revolution in technology that has made it possible to decipher the human genome. Epigenetics explains the capability gene expression regulation without modifying the genetic sequence. Epigenetic mechanisms are rooted changes in molecules, or nuclear characteristics that can alter gene expression without altering the sequences of DNA, i.e. DNA methylation, histone modification, and non-coding RNAs. Learning of the fundamental epigenetic modification allowing gene expression as well as cellular phenotype are advanced that novel insights into the epigenetic control of cardiovascular disease, hepatic disease, as well as chronic kidney disease are now emerging. From a half of century ago, in human disease the role of epigenetics has been considered. This subject has attracted many interests in the past decade, especially in complicated diseases like cardiovascular disease, hepatic disease as well as chronic kidney disease. This review first illustrates the history and classification of epigenetic modifications and the factors (i.e. genetic, environment, dietary, thought process and lifestyle) affecting to the epigenetics mechanisms. Likewise, the epigenetics role in human diseases is think out by targeting on some diseases and at the end, we have given the future perspective of this field. This review article provides concepts with some examples to describe a broad view of distinct aspects of epigenetics in biology and human diseases. Keywords: - Epigenetics, DNA methylation, Histone modifications, microRNAs and Gene expression and Disease.

scholarly journals Effects of cytochalasin B on DNA methylation and histone modification in parthenogenetically activated porcine embryos

Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 519-527 ◽  
Author(s):  
Xiaoxiao Hou ◽  
Jun Liu ◽  
Zhiren Zhang ◽  
Yanhui Zhai ◽  
Yutian Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Histone Modification ◽  
Actin Polymerization ◽  
Cytochalasin B ◽  
Epigenetic Modification ◽  
Cell Activity ◽  
Cleavage Rate ◽  
Expression Levels ◽  
Mammalian Embryos

DNA methylation and histone modification play important roles in the development of mammalian embryos. Cytochalasin B (CB) is an actin polymerization inhibitor that can significantly affect cell activity and is often used in studies concerning cytology. In recent years, CB is also commonly being used inin vitroexperiments on mammalian embryos, but few studies have addressed the effect of CB on the epigenetic modification of embryonic development, and the mechanism underlying this process is also unknown. This study was conducted to investigate the effects of CB on DNA methylation and histone modification in the development of parthenogenetically activated porcine embryos. Treatment with 5 μg/mL CB for 4 h significantly increased the cleavage rate, blastocyst rate and total cell number of blastocysts. However, the percentage of apoptotic cells and the expression levels of the apoptosis-related genesBCL-XL,BAXandCASP3were significantly decreased. Treatment with CB significantly decreased the expression levels ofDNMT1,DNMT3a,DNMT3b,HAT1andHDAC1at the pronuclear stage and promoted the conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). After CB treatment, the level of AcH3K9 was upregulated and the level of H3K9me3 was downregulated. When combined with Scriptaid and 5-Aza-Cdr, CB further improved the embryonic development competence and decreased the expression ofBCL-XL,BAXandCASP3. In conclusion, these results suggest that CB could improve embryonic development and the quality of the blastocyst by improving the epigenetic modification during the development of parthenogenetically activated embryos.

scholarly journals MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1214 ◽  
Author(s):  
Mohammad Mijanur Rahman ◽  
Andrew C. Brane ◽  
Trygve O. Tollefsbol
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Genomic Instability ◽  
Therapeutic Intervention ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Cancer Hallmarks ◽  
Cancer Pathogenesis

Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast cancer leads to mutations, copy number variations, and genetic rearrangements, while epigenetic remodeling involves alteration by DNA methylation, histone modification and microRNAs (miRNAs) of gene expression profiles. The accrued scientific findings strongly suggest epigenetic dysregulation in breast cancer pathogenesis though genomic instability is central to breast cancer hallmarks. Being reversible and plastic, epigenetic processes appear more amenable toward therapeutic intervention than the more unidirectional genetic alterations. In this review, we discuss the epigenetic reprogramming associated with breast cancer such as shuffling of DNA methylation, histone acetylation, histone methylation, and miRNAs expression profiles. As part of this, we illustrate how epigenetic instability orchestrates the attainment of cancer hallmarks which stimulate the neoplastic transformation-tumorigenesis-malignancy cascades. As reversibility of epigenetic controls is a promising feature to optimize for devising novel therapeutic approaches, we also focus on the strategies for restoring the epistate that favor improved disease outcome and therapeutic intervention.

scholarly journals Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives

RSC Advances ◽  
2018 ◽  
Vol 8 (52) ◽  
pp. 29714-29744 ◽  
Author(s):  
Muhammad Younas ◽  
Christophe Hano ◽  
Nathalie Giglioli-Guivarc'h ◽  
Bilal Haider Abbasi
Keyword(s):  
Breast Cancer ◽  
Current Understanding ◽  
Future Perspectives

Breast cancer is one of the most commonly diagnosed cancers around the globe and accounts for a large proportion of fatalities in women.

scholarly journals Glucose-induced, duration-dependent genome-wide DNA methylation changes in human endothelial cells

2020 ◽  
Vol 319 (2) ◽  
pp. C268-C276
Author(s):  
Erfan Aref-Eshghi ◽  
Saumik Biswas ◽  
Charlie Chen ◽  
Bekim Sadikovic ◽  
Subrata Chakrabarti
Keyword(s):  
Dna Methylation ◽  
Endothelial Cells ◽  
Embryonic Development ◽  
Cellular Differentiation ◽  
Hox Genes ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Epigenetic Mechanism ◽  
Dna Hypermethylation ◽  
Gene Expressions

DNA methylation, a critical epigenetic mechanism, plays an important role in governing gene expressions during biological processes such as aging, which is well known to be accelerated in hyperglycemia (diabetes). In the present study, we investigated the effects of glucose on whole genome DNA methylation in small [human retinal microvascular endothelial cells (HRECs)] and large [human umbilical vein endothelial cells (HUVECs)] vessel endothelial cell (EC) lines exposed to basal or high glucose-containing media for variable lengths of time. Using the Infinium EPIC array, we obtained 773,133 CpG sites (probes) for analysis. Unsupervised clustering of the top 5% probes identified four distinct clusters within EC groups, with significant methylation differences attributed to EC types and the duration of cell culture rather than glucose stimuli alone. When comparing the ECs incubated for 2 days versus 7 days, hierarchical clustering analyses [methylation change >10% and false discovery rate (FDR) <0.05] identified 17,354 and 128 differentially methylated CpGs for HUVECs and HRECs, respectively. Predominant DNA hypermethylation was associated with the length of culture and was enriched for gene enhancer elements and regions surrounding CpG shores and shelves. We identified 88 differentially methylated regions (DMRs) for HUVECs and 8 DMRs for HRECs (all FDR <0.05). Pathway enrichment analyses of DMRs highlighted involvement of regulators of embryonic development (i.e., HOX genes) and cellular differentiation [transforming growth factor-β (TGF-β) family members]. Collectively, our findings suggest that DNA methylation is a complex process that involves tightly coordinated, cell-specific mechanisms. Such changes in methylation overlap genes critical for cellular differentiation and embryonic development.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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