scholarly journals A novel cancer-germline transcript carrying pro-metastatic miR-105 andTET-targeting miR-767 induced by DNA hypomethylation in tumors

Epigenetics ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. 1163-1171 ◽  
Author(s):  
Axelle Loriot ◽  
Aurélie Van Tongelen ◽  
Jordi Blanco ◽  
Simon Klaessens ◽  
Julie Cannuyer ◽  
...  
Keyword(s):  
Dna Hypomethylation ◽  
Germline Transcript ◽  
Cancer Germline

scholarly journals Coordinated Cancer Germline Antigen Promoter and Global DNA Hypomethylation in Ovarian Cancer: Association with the BORIS/CTCF Expression Ratio and Advanced Stage

2011 ◽  
Vol 17 (8) ◽  
pp. 2170-2180 ◽  
Author(s):  
Anna Woloszynska-Read ◽  
Wa Zhang ◽  
Jihnhee Yu ◽  
Petra A. Link ◽  
Paulette Mhawech-Fauceglia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Stage ◽  
Dna Hypomethylation ◽  
Expression Ratio ◽  
Cancer Germline

Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes

2017 ◽  
Vol 396 ◽  
pp. 130-137 ◽  
Author(s):  
Aurélie Van Tongelen ◽  
Axelle Loriot ◽  
Charles De Smet
Keyword(s):  
Dna Hypomethylation ◽  
Germline Genes ◽  
Cancer Germline

scholarly journals Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2392
Author(s):  
Giovanna Spatari ◽  
Alessandro Allegra ◽  
Mariella Carrieri ◽  
Giovanni Pioggia ◽  
Sebastiano Gangemi
Keyword(s):  
Tumor Suppressor ◽  
Cpg Islands ◽  
Hematologic Malignancies ◽  
Genetic Alterations ◽  
Dna Hypomethylation ◽  
Negative Effects ◽  
Promoter Regions ◽  
Hematological Neoplasms ◽  
Altered Gene ◽  
Hematological Tumors

Benzene carcinogenic ability has been reported, and chronic exposure to benzene can be one of the risk elements for solid cancers and hematological neoplasms. Benzene is acknowledged as a myelotoxin, and it is able to augment the risk for the onset of acute myeloid leukemia, myelodysplastic syndromes, aplastic anemia, and lymphomas. Possible mechanisms of benzene initiation of hematological tumors have been identified, as a genotoxic effect, an action on oxidative stress and inflammation and the provocation of immunosuppression. However, it is becoming evident that genetic alterations and the other causes are insufficient to fully justify several phenomena that influence the onset of hematologic malignancies. Acquired epigenetic alterations may participate with benzene leukemogenesis, as benzene may affect nuclear receptors, and provoke post-translational alterations at the protein level, thereby touching the function of regulatory proteins, comprising oncoproteins and tumor suppressor proteins. DNA hypomethylation correlates with stimulation of oncogenes, while the hypermethylation of CpG islands in promoter regions of specific tumor suppressor genes inhibits their transcription and stimulates the onset of tumors. The discovery of the systems of epigenetic induction of benzene-caused hematological tumors has allowed the possibility to operate with pharmacological interventions able of stopping or overturning the negative effects of benzene.

scholarly journals Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raimonda Kubiliute ◽  
Indre Januskeviciene ◽  
Ruta Urbanaviciute ◽  
Kristina Daniunaite ◽  
Monika Drobniene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Protein Level ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Common Mechanism ◽  
Dna Hypomethylation ◽  
Mesenchymal Transition ◽  
Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

scholarly journals The chromosomal protein SMCHD1 regulates DNA methylation and the 2c-like state of embryonic stem cells by antagonizing TET proteins

2021 ◽  
Vol 7 (4) ◽  
pp. eabb9149
Author(s):  
Zhijun Huang ◽  
Jiyoung Yu ◽  
Wei Cui ◽  
Benjamin K. Johnson ◽  
Kyunggon Kim ◽  
...  
Keyword(s):  
Es Cells ◽  
Embryonic Stem ◽  
Homeobox Gene ◽  
Dna Demethylation ◽  
Chromosomal Protein ◽  
Dna Hypomethylation ◽  
Tet Proteins ◽  
Target Sites ◽  
Structural Maintenance Of Chromosomes ◽  
Hinge Domain

5-Methylcytosine (5mC) oxidases, the ten-eleven translocation (TET) proteins, initiate DNA demethylation, but it is unclear how 5mC oxidation is regulated. We show that the protein SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1) is found in complexes with TET proteins and negatively regulates TET activities. Removal of SMCHD1 from mouse embryonic stem (ES) cells induces DNA hypomethylation, preferentially at SMCHD1 target sites and accumulation of 5-hydroxymethylcytosine (5hmC), along with promoter demethylation and activation of the Dux double-homeobox gene. In the absence of SMCHD1, ES cells acquire a two-cell (2c) embryo–like state characterized by activation of an early embryonic transcriptome that is substantially imposed by Dux. Using Smchd1/Tet1/Tet2/Tet3 quadruple-knockout cells, we show that DNA demethylation, activation of Dux, and other genes upon SMCHD1 loss depend on TET proteins. These data identify SMCHD1 as an antagonist of the 2c-like state of ES cells and of TET-mediated DNA demethylation.

scholarly journals Epigenetic Contribution and Genomic Imprinting Dlk1-Dio3 miRNAs in Systemic Lupus Erythematosus

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 680
Author(s):  
Rujuan Dai ◽  
Zhuang Wang ◽  
S. Ansar Ahmed
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Methylation Status ◽  
Transcriptional Level ◽  
Dna Hypomethylation ◽  
Systemic Lupus ◽  
Multiple Organs ◽  
Genetic Imprinting

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that afflicts multiple organs, especially kidneys and joints. In addition to genetic predisposition, it is now evident that DNA methylation and microRNAs (miRNAs), the two major epigenetic modifications, are critically involved in the pathogenesis of SLE. DNA methylation regulates promoter accessibility and gene expression at the transcriptional level by adding a methyl group to 5′ cytosine within a CpG dinucleotide. Extensive evidence now supports the importance of DNA hypomethylation in SLE etiology. miRNAs are small, non-protein coding RNAs that play a critical role in the regulation of genome expression. Various studies have identified the signature lupus-related miRNAs and their functional contribution to lupus incidence and progression. In this review, the mutual interaction between DNA methylation and miRNAs regulation in SLE is discussed. Some lupus-associated miRNAs regulate DNA methylation status by targeting the DNA methylation enzymes or methylation pathway-related proteins. On the other hand, DNA hyper- and hypo-methylation are linked with dysregulated miRNAs expression in lupus. Further, we specifically discuss the genetic imprinting Dlk1-Dio3 miRNAs that are subjected to DNA methylation regulation and are dysregulated in several autoimmune diseases, including SLE.

scholarly journals The Temporal Order of DNA Replication Shaped by Mammalian DNA Methyltransferases

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 266
Author(s):  
Shin-ichiro Takebayashi ◽  
Tyrone Ryba ◽  
Kelsey Wimbish ◽  
Takuya Hayakawa ◽  
Morito Sakaue ◽  
...  
Keyword(s):  
Dna Replication ◽  
Temporal Order ◽  
Expression System ◽  
Embryonic Stem ◽  
Replication Timing ◽  
Dna Methyltransferases ◽  
Dna Hypomethylation ◽  
Transcriptional Changes ◽  
A Cell ◽  
Genomic Regions

Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the contexts of development and disease. DNA methylation by DNA methyltransferases (Dnmts) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell-based and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various Dnmt-mutant mouse embryonic stem (ES) cell lines that included a cell line with a drug-inducible Dnmt3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) was shown to be correlated with redistribution of H3K27me3 induced by DNA hypomethylation: Later replicating PH coincided with H3K27me3-enriched regions. In contrast, this relationship with H3K27me3 was not evident within chromosomal arm regions undergoing either early-to-late (EtoL) or late-to-early (LtoE) switching of replication timing upon loss of the Dnmts. Interestingly, Dnmt-sensitive transcriptional up- and downregulation frequently coincided with earlier and later shifts in replication timing of the chromosomal arm regions, respectively. Our study revealed the previously unrecognized complex and diverse effects of the Dnmts loss on the mammalian DNA replication landscape.

scholarly journals Role of Chronic Alcoholism Causing Cancer in Omnivores and Vegetarians through Epigenetic Modifications

2020 ◽  
Vol 07 (03) ◽  
pp. 080-086
Author(s):  
Syed Aaquil Hasan Syed Javid Hasan ◽  
Raisa Arifanie O'Zelian Pawirotaroeno ◽  
Syed Abrar Hasan Syed Javid Hasan ◽  
Elene Abzianidze
Keyword(s):  
Folate Deficiency ◽  
Chronic Alcoholism ◽  
Epigenetic Modifications ◽  
Alcohol Metabolism ◽  
Dna Hypomethylation ◽  
Contributing Factors ◽  
Vitamin Deficiencies ◽  
Adenosyl Methionine ◽  
And Oxidative Stress

AbstractOne of the significant consequences of alcohol consumption is cancer formation via several contributing factors such as action of alcohol metabolites, vitamin deficiencies, and oxidative stress. All these factors have been shown to cause epigenetic modifications via DNA hypomethylation, thus forming a basis for cancer development. Several published reviews and studies were systematically reviewed. Omnivores and vegetarians differ in terms of nutritional intake and deficiencies. As folate deficiency was found to be common among the omnivores, chronic alcoholism could possibly cause damage and eventually cancer in an omnivorous individual via DNA hypomethylation due to folate deficiency. Furthermore, as niacin was found to be deficient among vegetarians, damage in vegetarian chronic alcoholics could be due to increased NADH/NAD+ ratio, thus slowing alcohol metabolism in liver leading to increased alcohol and acetaldehyde which inhibit methyltransferase enzymes, eventually leading to DNA hypomethylation. Hence correcting the concerned deficiency and supplementation with S-adenosyl methionine could prove to be protective in chronic alcohol use.

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