scholarly journals Epigenetic Biomarkers for the Diagnosis and Treatment of Liver Disease

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1265
Author(s):  
María Arechederra ◽  
Miriam Recalde ◽  
María Gárate-Rascón ◽  
Maite G. Fernández-Barrena ◽  
Matías A. Ávila ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Liver Disease ◽  
Therapeutic Strategy ◽  
Therapeutic Strategies ◽  
Epigenetic Alterations ◽  
Post Translational Modifications ◽  
Epigenetic Marks ◽  
Diagnosis And Prognosis ◽  
Epigenetic Biomarkers ◽  
Non Coding Rna

Research in the last decades has demonstrated the relevance of epigenetics in controlling gene expression to maintain cell homeostasis, and the important role played by epigenome alterations in disease development. Moreover, the reversibility of epigenetic marks can be harnessed as a therapeutic strategy, and epigenetic marks can be used as diagnosis biomarkers. Epigenetic alterations in DNA methylation, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) expression have been associated with the process of hepatocarcinogenesis. Here, we summarize epigenetic alterations involved in the pathogenesis of chronic liver disease (CLD), particularly focusing on DNA methylation. We also discuss their utility as epigenetic biomarkers in liquid biopsy for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Finally, we discuss the potential of epigenetic therapeutic strategies for HCC treatment.

scholarly journals Epigenetic Biomarkers in Head and Neck Cancer

2018 ◽  
Vol 1 (2) ◽  
pp. 41-50 ◽  
Author(s):  
Shilpi Gupta ◽  
Prabhat Kumar ◽  
Jayant Maini ◽  
Harsimrut Kaur
Keyword(s):  
Risk Factors ◽  
Dna Methylation ◽  
Head And Neck ◽  
Current Knowledge ◽  
Human Papillomaviruses ◽  
Epigenetic Mechanisms ◽  
Definite Diagnosis ◽  
Diagnosis And Prognosis ◽  
Epigenetic Biomarkers ◽  
Non Coding Rna

Head and neck cancers (HNCs) are the most prevalent and aggressive type of cancers. Genetic, epigenetic, environmental and viral risk-factors are associated with HNC carcinogenesis. Persistent infection of oncogenic human papillomaviruses (HR-HPVs) represent distinct biological, molecular and epigenetic entities in HNCs. There are three main epigenetic mechanisms that regulate transcription, these are DNA methylation, histone modifications and alteration in non-coding RNA networks, which can dissected to identify innovative and accurate epigenetic biomarkers for diagnosis and prognosis of HNC patients. Due to the lacunae of accurate distinctive biomarkers for the definite diagnosis of HNC, the identification of predictive epigenetic markers is necessary that might modify or increase HNC patient’s survival. In this mini review, we briefly summarize the current knowledge of different epigenetic biomarkers in HNC.

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>

scholarly journals The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia

2019 ◽  
Vol 20 (11) ◽  
pp. 2837 ◽  
Author(s):  
Clara Apicella ◽  
Camino S. M. Ruano ◽  
Céline Méhats ◽  
Francisco Miralles ◽  
Daniel Vaiman
Keyword(s):  
Maternal Blood ◽  
Placental Development ◽  
Post Translational Modifications ◽  
Epigenetic Marks ◽  
Placental Function ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna ◽  
Potential Use

In this review, we comprehensively present the function of epigenetic regulations in normal placental development as well as in a prominent disease of placental origin, preeclampsia (PE). We describe current progress concerning the impact of DNA methylation, non-coding RNA (with a special emphasis on long non-coding RNA (lncRNA) and microRNA (miRNA)) and more marginally histone post-translational modifications, in the processes leading to normal and abnormal placental function. We also explore the potential use of epigenetic marks circulating in the maternal blood flow as putative biomarkers able to prognosticate the onset of PE, as well as classifying it according to its severity. The correlation between epigenetic marks and impacts on gene expression is systematically evaluated for the different epigenetic marks analyzed.

scholarly journals DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6354
Author(s):  
Inês Faleiro ◽  
Vânia Palma Roberto ◽  
Secil Demirkol Canli ◽  
Nicolas A. Fraunhoffer ◽  
Juan Iovanna ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Methylation Status ◽  
Therapeutic Targets ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Diagnostic Tools ◽  
Akt Pathway ◽  
Epigenetic Alterations ◽  
Epigenetic Biomarkers

Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients’ clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.

scholarly journals Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers

2021 ◽  
Vol 18 (4) ◽  
pp. 1883
Author(s):  
José Luis García-Giménez ◽  
Salvador Mena-Molla ◽  
Francisco José Tarazona-Santabalbina ◽  
Jose Viña ◽  
Mari Carmen Gomez-Cabrera ◽  
...  
Keyword(s):  
Histone Variants ◽  
Cellular Level ◽  
Older Individuals ◽  
Altered Expression ◽  
Post Translational Modifications ◽  
Adverse Health Outcomes ◽  
Epigenetic Biomarkers ◽  
Health Trajectories ◽  
Non Coding Rna ◽  
Core Histones

The main epigenetic features in aging are: reduced bulk levels of core histones, altered pattern of histone post-translational modifications, changes in the pattern of DNA methylation, replacement of canonical histones with histone variants, and altered expression of non-coding RNA. The identification of epigenetic mechanisms may contribute to the early detection of age-associated subclinical changes or deficits at the molecular and/or cellular level, to predict the development of frailty, or even more interestingly, to improve health trajectories in older adults. Frailty reflects a state of increased vulnerability to stressors as a result of decreased physiologic reserves, and even dysregulation of multiple physiologic systems leading to adverse health outcomes for individuals of the same chronological age. A key approach to overcome the challenges of frailty is the development of biomarkers to improve early diagnostic accuracy and to predict trajectories in older individuals. The identification of epigenetic biomarkers of frailty could provide important support for the clinical diagnosis of frailty, or more specifically, to the evaluation of its associated risks. Interventional studies aimed at delaying the onset of frailty and the functional alterations associated with it, would also undoubtedly benefit from the identification of frailty biomarkers. Specific to the article yet reasonably common within the subject discipline.

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 Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes

2012 ◽  
Vol 71 (2) ◽  
pp. 276-283 ◽  
Author(s):  
J. Alfredo Martínez ◽  
Paúl Cordero ◽  
Javier Campión ◽  
Fermín I. Milagro
Keyword(s):  
Nutritional Interventions ◽  
Nutritional Programming ◽  
Diagnosis And Prognosis ◽  
Metabolic Functions ◽  
Epigenetic Biomarkers ◽  
Non Coding Rna ◽  
Pregnancy And Lactation ◽  
Covalent Modifications ◽  
Dietary Treatments ◽  
Methylation Patterns

The huge health burden accompanying obesity is not only attributable to inadequate dietary and sedentary lifestyle habits, since a predisposing genetic make-up and other putative determinants concerning easier weight gain and fat deposition have been reported. Thus, several investigations aiming to understand energy metabolism and body composition maintenance have been performed considering the participation of perinatal nutritional programming and epigenetic processes as well as inflammation phenomena. The Developmental Origins of Health and Disease hypothesis and inheritance-oriented investigations concerning gene–nutrient interactions on energy homoeostasis and metabolic functions have suggested that inflammation could be not only a comorbidity of obesity but also a cause. There are several examples about the role of nutritional interventions in pregnancy and lactation, such as energetic deprivation, protein restriction and excess fat, which determine a cluster of disorders affecting energy efficiency in the offspring as well as different metabolic pathways, which are mediated by epigenetics encompassing the chromatin information encrypted by DNA methylation patterns, histone covalent modifications and non-coding RNA or microRNA. Epigenetic mechanisms may be boosted or impaired by dietary and environmental factors in the mother, intergenerationally or transiently transmitted, and could be involved in the obesity and inflammation susceptibility in the offspring. The aims currently pursued are the early identification of epigenetic biomarkers concerned in individual's disease susceptibility and the description of protocols for tailored dietary treatments/advice to counterbalance adverse epigenomic events. These approaches will allow diagnosis and prognosis implementation and facilitate therapeutic strategies in a personalised ‘epigenomically modelled’ manner to combat obesity and inflammation.

scholarly journals New Progress of Epigenetic Biomarkers in Urological Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Peng Wu ◽  
Ziyi Cao ◽  
Song Wu
Keyword(s):  
Dna Methylation ◽  
Early Diagnosis ◽  
Early Stage ◽  
Urinary System ◽  
Epigenetic Alterations ◽  
Mirna Regulation ◽  
Urological Cancer ◽  
Epigenetic Biomarkers ◽  
Urological Cancers ◽  
Specificity And Sensitivity

Urological cancers consist of bladder, kidney, prostate, and testis cancers and they are generally silenced at their early stage, which leads to the loss of the best opportunity for early diagnosis and treatment. Desired biomarkers are scarce for urological cancers and current biomarkers are lack of specificity and sensitivity. Epigenetic alterations are characteristic of nearly all kinds of human malignances including DNA methylation, histone modification, and miRNA regulation. Besides, the detection of these epigenetic conditions is easily accessible especially for urine, best target for monitoring the diseases of urinary system. Here, we summarize some new progress about epigenetic biomarkers in urological cancers, hoping to provide new thoughts for the diagnosis, treatment, and prognosis of urological cancers.

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.

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