Search results for "DNA methylation"
showing 10 items of 392 documents
Efficacy and epigenetic interactions of novel DNA hypomethylating agent guadecitabine (SGI-110) in preclinical models of hepatocellular carcinoma.
2016
ABSTRACT Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine. Here we found that guadecitabine i…
DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon…
2019
Aim: To investigate the genome-wide methylation of genetically characterized colorectal cancer stem cell (CR-CSC) lines. Materials & methods: Eight CR-CSC lines were isolated from primary colorectal cancer (CRC) tissues, cultured and characterized for aneuploidy, mutational status of CRC-related genes and microsatellite instability (MSI). Genome-wide DNA methylation was assessed by MethylationEPIC microarray. Results: We describe a distinctive methylation pattern that is maintained following in vivo passages in immune-compromised mice. We identified an epigenetic CR-CSC signature associated with MSI. We noticed that the preponderance of the differentially methylated positions do not re…
Epigenetic biomarkers for human sepsis and septic shock: insights from immunosuppression
2020
Sepsis is a life-threatening condition that occurs when the body responds to an infection damaging its own tissues. Sepsis survivors sometimes suffer from immunosuppression increasing the risk of death. To our best knowledge, there is no ‘gold standard’ for defining immunosuppression except for a composite clinical end point. As the immune system is exposed to epigenetic changes during and after sepsis, research that focuses on identifying new biomarkers to detect septic patients with immunoparalysis could offer new epigenetic-based strategies to predict short- and long-term pathological events related to this life-threatening state. This review describes the most relevant epigenetic mecha…
Impact of glucocorticoids on systemic sirtuin 1 expression and activity in rats with adjuvant-induced arthritis
2020
The class III histone deacetylase sirtuin 1 (SIRT1) plays a pivotal role in numerous biological and physiological functions, including inflammation. An association between SIRT1 and proinflammatory cytokines might exist. In addition to their important role in inflammation associated with rheumatoid arthritis (RA), proinflammatory cytokines mediate the development of systemic effects. Here, we evaluated systemic SIRT1 expression and enzymatic activity, in peripheral blood mononuclear cells (PBMCs) and in liver isolated from rats with adjuvant-induced arthritis (AIA), treated or not with low or high doses of glucocorticoids (GCs). We also measured the production of tumour necrosis factor alph…
Interrelationship between miRNA and splicing factors in pancreatic ductal adenocarcinoma
2021
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of diagnosis at late stage and inherent/acquired chemoresistance. Recent advances in genomic profiling and biology of this disease have not yet been translated to a relevant improvement in terms of disease management and patient’s survival. However, new possibilities for treatment may emerge from studies on key epigenetic factors. Deregulation of microRNA (miRNA) dependent gene expression and mRNA splicing are epigenetic processes that modulate the protein repertoire at the transcriptional level. These processes affect all aspects of PDAC pathogenesis and have great potential to unravel new therapeutic targets…
IL‐10‐producing B cells are characterized by a specific methylation signature
2019
Among the family of regulatory B cells, the subset able to produce interleukin-10 (IL-10) is the most studied, yet its biology is still a matter of investigation. The DNA methylation profiling of the il-10 gene locus revealed a novel epigenetic signature characterizing murine B cells ready to respond through IL-10 synthesis: a demethylated region located 4.5 kb from the transcription starting site (TSS), that we named early IL10 regulatory region (eIL10rr). This feature allows to distinguish B cells that are immediately prone and developmentally committed to IL-10 production from those that require a persistent stimulation to exert an IL-10-mediated regulatory function. These late IL-10 pro…
A new parallel pipeline for DNA methylation analysis of long reads datasets
2017
Background DNA methylation is an important mechanism of epigenetic regulation in development and disease. New generation sequencers allow genome-wide measurements of the methylation status by reading short stretches of the DNA sequence (Methyl-seq). Several software tools for methylation analysis have been proposed over recent years. However, the current trend is that the new sequencers and the ones expected for an upcoming future yield sequences of increasing length, making these software tools inefficient and obsolete. Results In this paper, we propose a new software based on a strategy for methylation analysis of Methyl-seq sequencing data that requires much shorter execution times while…
On the Use of Binary Trees for DNA Hydroxymethylation Analysis
2017
DNA methylation (mC) and hydroxymethylation (hmC) can have a significant effect on normal human development, health and disease status. Hydroxymethylation studies require specific treatment of DNA, as well as software tools for their analysis. In this paper, we propose a parallel software tool for analyzing the DNA hydroxymethylation data obtained by TAB-seq. The software is based on the use of binary trees for searching the different occurrences of methylation and hydroxymethylation in DNA samples. The binary trees allow to efficiently store and access the information about the methylation of each methylated/hydroxymethylated cytosines in the samples. Evaluation results shows that the perf…
Inherent and toxicant-provoked reduction in DNA repair capacity: A key mechanism for personalized risk assessment, cancer prevention and intervention…
2018
Abstract Genomic investigations reveal novel evidence which indicates that genetic predisposition and inherent drug response are key factors for development of cancer and for poor response to therapy. However, mechanisms for these outcomes and interactions with environmental factors have not been well-characterized. Therefore, cancer risk, prevention, intervention and prognosis determinations have still mainly been based on population, rather than on individualized, evaluations. The objective of this review was to demonstrate that a key mechanism which contributes to the determination is inherent and/or toxicant-provoked reduction in DNA repair capacity. In addition, functional and quantita…
DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…
2016
Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…