Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications

Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.

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The Role of DNA Methylation and Histone Modification in Periodontal Disease: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms21176217 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6217

Author(s):

Ismael Khouly ◽

Rosalie Salus Braun ◽

Michelle Ordway ◽

Bradley Eric Aouizerat ◽

Iya Ghassib ◽

...

Keyword(s):

Systematic Review ◽

Dna Methylation ◽

Periodontal Disease ◽

Histone Modification ◽

Histone Modifications ◽

Disease Risk ◽

Periodontal Diseases ◽

Epigenetic Changes ◽

Human Adults

Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. IL6, IL6R, IFNG, PTGS2, SOCS1, and TNF were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.

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The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

International Journal of Molecular Sciences ◽

10.3390/ijms21030980 ◽

2020 ◽

Vol 21 (3) ◽

pp. 980 ◽

Cited By ~ 9

Author(s):

Yi-Chou Hou ◽

Chien-Lin Lu ◽

Tzu-Hang Yuan ◽

Min-Tser Liao ◽

Chia-Ter Chao ◽

...

Keyword(s):

Dna Methylation ◽

Histone Modification ◽

Vascular Calcification ◽

Calcium Deposition ◽

Non Coding Rna ◽

Physico Chemical ◽

Variable Combination ◽

Epigenetic Signatures ◽

Epigenetic Processes

Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.

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nc886, a Non-Coding RNA, Is a New Biomarker and Epigenetic Mediator of Cellular Senescence in Fibroblasts

International Journal of Molecular Sciences ◽

10.3390/ijms222413673 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13673

Author(s):

Yuna Kim ◽

Hyanggi Ji ◽

Eunae Cho ◽

Nok-Hyun Park ◽

Kyeonghwan Hwang ◽

...

Keyword(s):

Cellular Senescence ◽

Replicative Senescence ◽

Tumor Formation ◽

Epigenetic Changes ◽

Functional Studies ◽

Human Models ◽

Age Related ◽

Non Coding Rna ◽

Epigenetic Regulators

Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-β-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.

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Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Metabolites ◽

10.3390/metabo11080479 ◽

2021 ◽

Vol 11 (8) ◽

pp. 479

Author(s):

Elizabeth L. Lieu ◽

Neil Kelekar ◽

Pratibha Bhalla ◽

Jiyeon Kim

Keyword(s):

Metabolic Disease ◽

Inborn Errors Of Metabolism ◽

Metabolic Diseases ◽

Treatment Options ◽

Biochemical Properties ◽

Biological Molecules ◽

Diagnostic Tools ◽

Inborn Errors ◽

Mannose Metabolism

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview

Journal of Clinical Medicine ◽

10.3390/jcm10204786 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4786

Author(s):

Undine-Sophie Deumer ◽

Angelica Varesi ◽

Valentina Floris ◽

Gabriele Savioli ◽

Elisa Mantovani ◽

...

Keyword(s):

Cognitive Impairment ◽

Chronic Fatigue Syndrome ◽

Systemic Disease ◽

Disease Onset ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Diagnostic Tools ◽

Fatigue Syndrome ◽

Non Coding Rna

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS.

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The Role of Sulforaphane in Epigenetic Mechanisms, Including Interdependence between Histone Modification and DNA Methylation

International Journal of Molecular Sciences ◽

10.3390/ijms161226195 ◽

2015 ◽

Vol 16 (12) ◽

pp. 29732-29743 ◽

Cited By ~ 36

Author(s):

Agnieszka Kaufman-Szymczyk ◽

Grzegorz Majewski ◽

Katarzyna Lubecka-Pietruszewska ◽

Krystyna Fabianowska-Majewska

Keyword(s):

Dna Methylation ◽

Histone Modification ◽

Epigenetic Mechanisms

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The role of epigenetics in the pathology of diabetic complications

AJP Renal Physiology ◽

10.1152/ajprenal.00200.2010 ◽

2010 ◽

Vol 299 (1) ◽

pp. F14-F25 ◽

Cited By ~ 189

Author(s):

Louisa M. Villeneuve ◽

Rama Natarajan

Keyword(s):

Diabetic Complications ◽

Animal Studies ◽

Microvascular Complications ◽

Treatment Options ◽

Metabolic Memory ◽

Epigenetic Changes ◽

Methylation Patterns

Diabetes is associated with significantly accelerated rates of several debilitating microvascular complications such as nephropathy, retinopathy, and neuropathy, and macrovascular complications such as atherosclerosis and stroke. While several studies have been devoted to the evaluation of genetic factors related to type 1 and type 2 diabetes and associated complications, much less is known about epigenetic changes that occur without alterations in the DNA sequence. Environmental factors and nutrition have been implicated in diabetes and can also affect epigenetic states. Exciting research has shown that epigenetic changes in chromatin can affect gene transcription in response to environmental stimuli, and changes in key chromatin histone methylation patterns have been noted under diabetic conditions. Reports also suggest that epigenetics may be involved in the phenomenon of metabolic memory observed in clinic trials and animal studies. Further exploration into epigenetic mechanisms can yield new insights into the pathogenesis of diabetes and its complications and uncover potential therapeutic targets and treatment options to prevent the continued development of diabetic complications even after glucose control has been achieved.

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The role of microRNA in myelodysplastic syndromes: beyond DNA methylation and histone modification

European Journal Of Haematology ◽

10.1111/ejh.12735 ◽

2016 ◽

Vol 96 (6) ◽

pp. 553-563 ◽

Cited By ~ 4

Author(s):

Vibor Milunović ◽

Inga Mandac Rogulj ◽

Ana Planinc-Peraica ◽

Ekaterina Bulycheva ◽

Slobodanka Kolonić Ostojić

Keyword(s):

Dna Methylation ◽

Histone Modification ◽

Myelodysplastic Syndromes

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The diagnostic role of DNA methylation in sporadic endometrial cancer: a systematic review and meta-analysis

Oncotarget ◽

10.18632/oncotarget.23480 ◽

2017 ◽

Vol 9 (9) ◽

pp. 8642-8652 ◽

Cited By ~ 3

Author(s):

Yu Fan ◽

Yu Wang ◽

Shaozhi Fu ◽

Linglin Yang ◽

Sheng Lin ◽

...

Keyword(s):

Systematic Review ◽

Dna Methylation ◽

Endometrial Cancer ◽

Meta Analysis ◽

Diagnostic Role

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Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction

Diabetologia ◽

10.1007/s00125-019-05011-8 ◽

2019 ◽

Vol 62 (12) ◽

pp. 2171-2178 ◽

Cited By ~ 7

Author(s):

Hannah R. Elliott ◽

Gemma C. Sharp ◽

Caroline L. Relton ◽

Deborah A. Lawlor

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Gestational Diabetes ◽

Histone Modification ◽

Diabetes Research ◽

Epigenetic Mechanisms ◽

Epigenetic Epidemiology ◽

Epigenetic Biomarkers

Abstract Epigenetics encapsulates a group of molecular mechanisms including DNA methylation, histone modification and microRNAs (miRNAs). Gestational diabetes (GDM) increases the risk of adverse perinatal outcomes and is associated with future offspring risk of obesity and type 2 diabetes. It has been hypothesised that epigenetic mechanisms mediate an effect of GDM on offspring adiposity and type 2 diabetes and this could provide a modifiable mechanism to reduce type 2 diabetes in the next generation. Evidence for this hypothesis is lacking. Epigenetic epidemiology could also contribute to reducing type 2 diabetes by identifying biomarkers that accurately predict risk of GDM and its associated future adverse outcomes. We reviewed published human studies that explored associations between any of maternal GDM, type 2 diabetes, gestational fasting or post-load glucose and any epigenetic marker (DNA methylation, histone modification or miRNA). Of the 81 relevant studies we identified, most focused on the potential role of epigenetic mechanisms in mediating intrauterine effects of GDM on offspring outcomes. Studies were small (median total number of participants 58; median number of GDM cases 27) and most did not attempt replication. The most common epigenetic measure analysed was DNA methylation. Most studies that aimed to explore epigenetic mediation examined associations of in utero exposure to GDM with offspring cord or infant blood/placenta DNA methylation. Exploration of any causal effect, or effect on downstream offspring outcomes, was lacking. There is a need for more robust methods to explore the role of epigenetic mechanisms as possible mediators of effects of exposure to GDM on future risk of obesity and type 2 diabetes. Research to identify epigenetic biomarkers to improve identification of women at risk of GDM and its associated adverse (maternal and offspring) outcomes is currently rare but could contribute to future tools for accurate risk stratification.

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