scholarly journals Targeting Epigenetic Modifications in Uveal Melanoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5314
Author(s):  
Pooneh Chokhachi Baradaran ◽  
Zuzana Kozovska ◽  
Alena Furdova ◽  
Bozena Smolkova
Keyword(s):  
Dna Methylation ◽  
Uveal Melanoma ◽  
Histone Modifications ◽  
Tumor Suppressor Genes ◽  
Primary Therapy ◽  
Epigenetic Alterations ◽  
Combination Therapies ◽  
Non Coding Rna ◽  
Aberrant Dna Methylation ◽  
New Generation

Uveal melanoma (UM), the most common intraocular malignancy in adults, is a rare subset of melanoma. Despite effective primary therapy, around 50% of patients will develop the metastatic disease. Several clinical trials have been evaluated for patients with advanced UM, though outcomes remain dismal due to the lack of efficient therapies. Epigenetic dysregulation consisting of aberrant DNA methylation, histone modifications, and small non-coding RNA expression, silencing tumor suppressor genes, or activating oncogenes, have been shown to play a significant role in UM initiation and progression. Given that there is no evidence any approach improves results so far, adopting combination therapies, incorporating a new generation of epigenetic drugs targeting these alterations, may pave the way for novel promising therapeutic options. Furthermore, the fusion of effector enzymes with nuclease-deficient Cas9 (dCas9) in clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) system equips a potent tool for locus-specific erasure or establishment of DNA methylation as well as histone modifications and, therefore, transcriptional regulation of specific genes. Both, CRISPR-dCas9 potential for driver epigenetic alterations discovery, and possibilities for their targeting in UM are highlighted in this review.

scholarly journals Neuroblastoma and the epigenome

2021 ◽  
Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Disease Diagnosis ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Aberrant Expression ◽  
Tet Proteins ◽  
Relative Paucity ◽  
Underlying Causes ◽  
Aberrant Dna Methylation

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.

Cataloging recent advances in epigenetic alterations in major mental disorders and autism

Epigenomics ◽  
2021 ◽  
Author(s):  
Hamid Mostafavi Abdolmaleky ◽  
Jin-Rong Zhou ◽  
Sam Thiagalingam
Keyword(s):  
Dna Methylation ◽  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Drug Effects ◽  
Tissue Cell ◽  
Epigenetic Alterations ◽  
Cell Specificity ◽  
Aberrant Dna Methylation ◽  
Potential Origin

During the last two decades, diverse epigenetic modifications including DNA methylation, histone modifications, RNA editing and miRNA dysregulation have been associated with psychiatric disorders. A few years ago, in a review we outlined the most common epigenetic alterations in major psychiatric disorders (e.g., aberrant DNA methylation of DTNBP1, HTR2A, RELN, MB-COMT and PPP3CC, and increased expression of miR-34a and miR-181b). Recent follow-up studies have uncovered other DNA methylation aberrations affecting several genes in mental disorders, in addition to dysregulation of many miRNAs. Here, we provide an update on new epigenetic findings and highlight potential origin of the diversity and inconsistencies, focusing on drug effects, tissue/cell specificity of epigenetic landscape and discuss shortcomings of the current diagnostic criteria in mental disorders.

Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure

2010 ◽  
Vol 50 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Abdellah H. K. Ali ◽  
Kazuya Kondo ◽  
Toshiaki Namura ◽  
Yoshitaka Senba ◽  
Hiromitsu Takizawa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Lung Cancers ◽  
Aberrant Dna Methylation ◽  
Chromate Exposure

scholarly journals CRUCIAL CHALLENGES IN EPIGENETIC CANCER THERAPEUTIC STRATEGY YET TO BE RESOLVED

2016 ◽  
Vol 8 (12) ◽  
pp. 1 ◽  
Author(s):  
Md. Torequl Islam
Keyword(s):  
Dna Methylation ◽  
Therapeutic Strategy ◽  
Short Note ◽  
Therapeutic Interventions ◽  
Epigenetic Alterations ◽  
Genetic Pathways ◽  
Non Coding Rna ◽  
Small Ncrnas ◽  
Epigenetic Machinery ◽  
Novel Strategy

<p>Cancer is considered by both genetic and epigenetic pathways. Although, genetic pathways are straightforward, but the reversibility and numerous unclear talks make epigenetic pathway complicated. DNA methylation, histone modifications and non-coding RNA (ncRNA) mediated gene silencing are the three known consequences in epigenetic alterations. In this context, small ncRNAs such as microRNA are known to regulate various components of cellular epigenetic machinery by up or down-regulating in pathogenesis; those are already known in a number of pathophysiological states. These types of biomarkers can be used in the diagnosis and therapeutic interventions in some instances. Although some epigenetic therapies have been introduced, but a number of challenges in each case are remarkable, encouraging more researchers in this field of novel strategy. This paper will discuss a short note on epigenetics and epigenetic therapeutic interventions along with crucial challenges yet to be resolved.</p>

Methyl-CpG-binding proteins in cancer: blaming the DNA methylation messenger

2005 ◽  
Vol 83 (3) ◽  
pp. 374-384 ◽  
Author(s):  
Esteban Ballestar ◽  
Manel Esteller
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Binding Proteins ◽  
Excision Repair ◽  
Cpg Islands ◽  
Current Data ◽  
Epigenetic Alterations ◽  
Domain Family ◽  
Promoter Regions ◽  
Cancer Epigenetics

In recent years, epigenetic alterations have come to prominence in cancer research. In particular, hypermethylation of CpG islands located in the promoter regions of tumor-suppressor genes is now firmly established as an important mechanism for gene inactivation in cancer. One of the most remarkable achievements in the field has been the identification of the methyl-CpG-binding domain family of proteins, which provide mechanistic links between specific patterns of DNA methylation and histone modifications. Although many of the current data indicate that methyl-CpG-binding proteins play a key role in maintaining a transcriptionally inactive state of methylated genes, MBD4 is also known to be involved in excision repair of T:G mismatches. The latter is a member of this family of proteins and appears to play a role in reducing mutations at 5-methylcytosine. This review examines the contribution of methyl-CpG-binding proteins in the epigenetic pathway of cancer.Key words: methyl-CpG-binding, MeCP2, DNA methylation, Rett syndrome, cancer epigenetics.

scholarly journals Integration of sperm ncRNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel Beck ◽  
Millissia Ben Maamar ◽  
Michael K. Skinner
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Epigenetic Alterations ◽  
Adult Males ◽  
Transgenerational Inheritance ◽  
Non Coding Rna ◽  
F2 Generation ◽  
Genetic Form ◽  
F1 Generation ◽  
Epigenetic Processes

Abstract Background Environmentally induced epigenetic transgenerational inheritance of pathology and phenotypic variation has been demonstrated in all organisms investigated from plants to humans. This non-genetic form of inheritance is mediated through epigenetic alterations in the sperm and/or egg to subsequent generations. Although the combined regulation of differential DNA methylated regions (DMR), non-coding RNA (ncRNA), and differential histone retention (DHR) have been shown to occur, the integration of these different epigenetic processes remains to be elucidated. The current study was designed to examine the integration of the different epigenetic processes. Results A rat model of transiently exposed F0 generation gestating females to the agricultural fungicide vinclozolin or pesticide DDT (dichloro-diphenyl-trichloroethane) was used to acquire the sperm from adult males in the subsequent F1 generation offspring, F2 generation grand offspring, and F3 generation great-grand offspring. The F1 generation sperm ncRNA had substantial overlap with the F1, F2 and F3 generation DMRs, suggesting a potential role for RNA-directed DNA methylation. The DMRs also had significant overlap with the DHRs, suggesting potential DNA methylation-directed histone retention. In addition, a high percentage of DMRs induced in the F1 generation sperm were maintained in subsequent generations. Conclusions Many of the DMRs, ncRNA, and DHRs were colocalized to the same chromosomal location regions. Observations suggest an integration of DMRs, ncRNA, and DHRs in part involve RNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance.

scholarly journals Behavioral Epigenetics: Perspectives Based on Experience-Dependent Epigenetic Inheritance

Epigenomes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 18 ◽  
Author(s):  
You-Yuan Pang ◽  
Rita Jui-Hsien Lu ◽  
Pao-Yang Chen
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Animal Behavior ◽  
Noncoding Rna ◽  
Environmental Enrichment ◽  
Epigenetic Inheritance ◽  
Epigenetic Alterations ◽  
Molecular Processes ◽  
Regulate Gene Expression

Epigenetic regulation plays an important role in gene regulation, and epigenetic markers such as DNA methylation and histone modifications are generally described as switches that regulate gene expression. Behavioral epigenetics is defined as the study of how epigenetic alterations induced by experience and environmental stress may affect animal behavior. It studies epigenetic alterations due to environmental enrichment. Generally, molecular processes underlying epigenetic regulation in behavioral epigenetics include DNA methylation, post-translational histone modifications, noncoding RNA activity, and other unknown molecular processes. Whether the inheritance of epigenetic features will occur is a crucial question. In general, the mechanism underlying inheritance can be explained by two main phenomena: Germline-mediated epigenetic inheritance and interact epigenetic inheritance of somatic cells through germline. In this review, we focus on examining behavioral epigenetics based on its possible modes of inheritance and discuss the considerations in the research of epigenetic transgenerational inheritance.

Sign in / Sign up

Export Citation Format

Share Document