Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy

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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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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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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Faculty Opinions recommendation of The role of DNA methylation in the metabolic memory phenomenon associated with the continued progression of diabetic retinopathy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726891646.793527392 ◽

2017 ◽

Author(s):

Kathryn P Burdon

Keyword(s):

Dna Methylation ◽

Diabetic Retinopathy ◽

Metabolic Memory

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

International Journal of Molecular Sciences ◽

10.3390/ijms22052305 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2305

Author(s):

Futaba Inoue ◽

Kenbun Sone ◽

Yusuke Toyohara ◽

Yu Takahashi ◽

Asako Kukita ◽

...

Keyword(s):

Dna Methylation ◽

Endometrial Cancer ◽

Histone Modification ◽

Treatment Options ◽

Diagnostic Tools ◽

Epigenetic Changes ◽

Non Coding Rna ◽

Advanced Stages ◽

Epigenetic Regulators

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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Regulation of Canonical Oncogenic Signaling Pathways in Cancer via DNA Methylation

Cancers ◽

10.3390/cancers12113199 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3199

Author(s):

Jennifer Lu ◽

Premila Wilfred ◽

Darren Korbie ◽

Matt Trau

Keyword(s):

Dna Methylation ◽

Signaling Pathways ◽

Biomarker Discovery ◽

Oncogenic Signaling ◽

Tissue Samples ◽

Epigenetic Biomarkers ◽

Differentially Methylated Genes ◽

Oncogenic Signaling Pathways ◽

Integration Analysis

Disruption of signaling pathways that plays a role in the normal development and cellular homeostasis may lead to the dysregulation of cellular signaling and bring about the onset of different diseases, including cancer. In addition to genetic aberrations, DNA methylation also acts as an epigenetic modifier to drive the onset and progression of cancer by mediating the reversible transcription of related genes. Although the role of DNA methylation as an alternative driver of carcinogenesis has been well-established, the global effects of DNA methylation on oncogenic signaling pathways and the presentation of cancer is only emerging. In this article, we introduced a differential methylation parsing pipeline (MethylMine) which mined for epigenetic biomarkers based on feature selection. This pipeline was used to mine for biomarkers, which presented a substantial difference in methylation between the tumor and the matching normal tissue samples. Combined with the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis, we revisited the TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancer, and identified differentially methylated genes within the NRF2-KEAP1/PI3K oncogenic pathway, which regulates the expression of cytoprotective genes, that serve as potential therapeutic targets to treat different cancers.

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The Role of DNA Methylation in the Metabolic Memory Phenomenon Associated With the Continued Progression of Diabetic Retinopathy

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.16-19759 ◽

2016 ◽

Vol 57 (13) ◽

pp. 5748 ◽

Cited By ~ 26

Author(s):

Manish Mishra ◽

Renu A. Kowluru

Keyword(s):

Dna Methylation ◽

Diabetic Retinopathy ◽

Metabolic Memory

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Hypomethylation and downregulation of miR-23b-3p are associated with upregulated PLAU: a diagnostic and prognostic biomarker in head and neck squamous cell carcinoma

Cancer Cell International ◽

10.1186/s12935-021-02251-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zirong Huo ◽

Xiaoguang Li ◽

Jieyu Zhou ◽

Yuqin Fan ◽

Zhentao Wang ◽

...

Keyword(s):

Dna Methylation ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Signaling Pathways ◽

Squamous Cell ◽

Prognostic Biomarker ◽

Neck Squamous Cell Carcinoma ◽

Dna Hypomethylation

Abstract Background DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Although previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC). Methods Multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database and clinical samples were applied to evaluate the beneficial biomarkers in HNSCC. We focused on the role of plasminogen activator urokinase (PLAU), including diagnostic and prognostic significance, gene expression analysis, aberrant DNA methylation characteristics, interaction of miRNAs and associated signaling pathways. Results We found that PLAU was aberrantly upregulated in HNSCC, regardless of the mRNA or protein level. The results of receiver operating characteristic (ROC) curve and Cox regression analysis revealed that PLAU was a diagnostic and independent prognostic factor for patients with HNSCC. Hypomethylation of PLAU was closely related to poor survival in HNSCC. Additionally, miR-23b-3p was predicted to target PLAU and was significantly downregulated in HNSCC tissues. Therefore, our findings suggested that PLAU functioned as a promoter in the pathological process of HNSCC. DNA hypomethylation and downregulation of miR-23b-3p were associated with PLAU overexpression. Finally, our findings provided evidence of a significant interaction between PLAU-target and miRNAs-target pathways, indicating that miR-23b-3p suppresses malignant properties of HNSCC by targeting PLAU via Ras/MAPK and Akt/mTOR signaling pathways. Conclusions PLAU is overexpressed and may serve as an independent diagnostic and prognostic biomarker in HNSCC. Hypomethylation and downregulation of miR-23b-3p might account for the oncogenic role of PLAU in HNSCC.

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