scholarly journals O-GlcNAcylation links oncogenic signals and cancer epigenetics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lidong Sun ◽  
Suli Lv ◽  
Tanjing Song
Keyword(s):  
Cancer Therapy ◽  
Cancer Biology ◽  
Protein Modification ◽  
Epigenetic Modification ◽  
Wide Spectrum ◽  
Epigenetic Modifications ◽  
Enzymatic Reactions ◽  
Cancer Epigenetics ◽  
Substantial Impact ◽  
Single Enzyme

AbstractPrevalent dysregulation of epigenetic modifications plays a pivotal role in cancer. Targeting epigenetic abnormality is a new strategy for cancer therapy. Understanding how conventional oncogenic factors cause epigenetic abnormality is of great basic and translational value. O-GlcNAcylation is a protein modification which affects physiology and pathophysiology. In mammals, O-GlcNAcylation is catalyzed by one single enzyme OGT and removed by one single enzyme OGA. O-GlcNAcylation is affected by the availability of the donor, UDP-GlcNAc, generated by the serial enzymatic reactions in the hexoamine biogenesis pathway (HBP). O-GlcNAcylation regulates a wide spectrum of substrates including many proteins involved in epigenetic modification. Like epigenetic modifications, abnormality of O-GlcNAcylation is also common in cancer. Studies have revealed substantial impact on HBP enzymes and OGT/OGA by oncogenic signals. In this review, we will first summarize how oncogenic signals regulate HBP enzymes, OGT and OGA in cancer. We will then integrate this knowledge with the up to date understanding how O-GlcNAcylation regulates epigenetic machinery. With this, we propose a signal axis from oncogenic signals through O-GlcNAcylation dysregulation to epigenetic abnormality in cancer. Further elucidation of this axis will not only advance our understanding of cancer biology but also provide new revenues towards cancer therapy.

scholarly journals Genome of a citrus rootstock and global DNA demethylation caused by heterografting

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yue Huang ◽  
Yuantao Xu ◽  
Xiaolin Jiang ◽  
Huiwen Yu ◽  
Huihui Jia ◽  
...  
Keyword(s):  
Sweet Orange ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Genetic Effects ◽  
Dna Demethylation ◽  
Poncirus Trifoliata ◽  
Protein Coding ◽  
Horticultural Crops ◽  
Citrus Rootstock ◽  
Methylome Analysis

AbstractGrafting is an ancient technique used for plant propagation and improvement in horticultural crops for at least 1,500 years. Citrus plants, with a seed-to-seed cycle of 5–15 years, are among the fruit crops that were probably domesticated by grafting. Poncirus trifoliata, a widely used citrus rootstock, can promote early flowering, strengthen stress tolerance, and improve fruit quality via scion–rootstock interactions. Here, we report its genome assembly using PacBio sequencing. We obtained a final genome of 303 Mb with a contig N50 size of 1.17 Mb and annotated 25,680 protein-coding genes. DNA methylome and transcriptome analyses indicated that the strong adaptability of P. trifoliata is likely attributable to its special epigenetic modification and expression pattern of resistance-related genes. Heterografting by using sweet orange as scion and P. trifoliata as rootstock and autografting using sweet orange as both scion and rootstock were performed to investigate the genetic effects of the rootstock. Single-base methylome analysis indicated that P. trifoliata as a rootstock caused DNA demethylation and a reduction in 24-nt small RNAs (sRNAs) in scions compared to the level observed with autografting, implying the involvement of sRNA-mediated graft-transmissible epigenetic modifications in citrus grafting. Taken together, the assembled genome for the citrus rootstock and the analysis of graft-induced epigenetic modifications provide global insights into the genetic effects of rootstock–scion interactions and grafting biology.

scholarly journals Metabolic reprogramming and epigenetic modifications on the path to cancer

2021 ◽  
Author(s):  
Linchong Sun ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Immune Cells ◽  
Immune Escape ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Metabolic Reprogramming ◽  
Epigenetic Alterations ◽  
Metabolic Alterations ◽  
Cancer Hallmarks ◽  
Epigenetic Remodeling ◽  
Spatial Regionalization

AbstractMetabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.

scholarly journals Mitochondrial DNA Methylation and Human Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4594
Author(s):  
Andrea Stoccoro ◽  
Fabio Coppedè
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Nuclear Genome ◽  
Epigenetic Modifications ◽  
Human Diseases ◽  
Loop Region ◽  
D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

Nutritional Status Impacts Epigenetic Regulation in Early Embryo Development: A Scoping Review

2021 ◽  
Author(s):  
Shuang Cai ◽  
Shuang Quan ◽  
Guangxin Yang ◽  
Meixia Chen ◽  
Qianhong Ye ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Embryo Development ◽  
Epigenetic Regulation ◽  
Scoping Review ◽  
Epigenetic Modification ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Epigenetic Modifications ◽  
Nutrition Status ◽  
Early Embryo Development

ABSTRACTWith the increasing maternal age and the use of assisted reproductive technology in various countries worldwide, the influence of epigenetic modification on embryonic development is increasingly notable and prominent. Epigenetic modification disorders caused by various nutritional imbalance would cause embryonic development abnormalities and even have an indelible impact on health in adulthood. In this scoping review, we summarize the main epigenetic modifications in mammals and the synergies among different epigenetic modifications, especially DNA methylation, histone acetylation, and histone methylation. We performed an in-depth analysis of the regulation of various epigenetic modifications on mammals from zygote formation to cleavage stage and blastocyst stage, and reviewed the modifications of key sites and their potential molecular mechanisms. In addition, we discuss the effects of nutrition (protein, lipids, and one-carbon metabolism) on epigenetic modification in embryos and emphasize the importance of various nutrients in embryonic development and epigenetics during pregnancy. Failures in epigenetic regulation have been implicated in mammalian and human early embryo loss and disease. With the use of reproductive technologies, it is becoming even more important to establish developmentally competent embryos. Therefore, it is essential to evaluate the extent to which embryos are sensitive to these epigenetic modifications and nutrition status. Understanding the epigenetic regulation of early embryo development will help us make better use of reproductive technologies and nutrition regulation to improve reproductive health in mammals.

scholarly journals Cancer Epigenetics: New Therapies and New Challenges

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Eleftheria Hatzimichael ◽  
Tim Crook
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Hdac Inhibitors ◽  
Clinical Impact ◽  
Clinical Use ◽  
Cancer Epigenetics ◽  
Dnmt Inhibitors ◽  
Epigenetic Effects ◽  
New Challenges ◽  
Neoplastic Disorders

Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers.

scholarly journals Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 126
Author(s):  
Julio Plaza-Diaz ◽  
David Izquierdo ◽  
Álvaro Torres-Martos ◽  
Aiman Tariq Baig ◽  
Concepción M. Aguilera ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Gene Transcription ◽  
Histone Modifications ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Late Response ◽  
Transcriptional Responses ◽  
Response To Exercise ◽  
The Impact

Exercise and physical activity induces physiological responses in organisms, and adaptations in skeletal muscle, which is beneficial for maintaining health and preventing and/or treating most chronic diseases. These adaptations are mainly instigated by transcriptional responses that ensue in reaction to each individual exercise, either resistance or endurance. Consequently, changes in key metabolic, regulatory, and myogenic genes in skeletal muscle occur as both an early and late response to exercise, and these epigenetic modifications, which are influenced by environmental and genetic factors, trigger those alterations in the transcriptional responses. DNA methylation and histone modifications are the most significant epigenetic changes described in gene transcription, linked to the skeletal muscle transcriptional response to exercise, and mediating the exercise adaptations. Nevertheless, other alterations in the epigenetics markers, such as epitranscriptomics, modifications mediated by miRNAs, and lactylation as a novel epigenetic modification, are emerging as key events for gene transcription. Here, we provide an overview and update of the impact of exercise on epigenetic modifications, including the well-described DNA methylations and histone modifications, and the emerging modifications in the skeletal muscle. In addition, we describe the effects of exercise on epigenetic markers in other metabolic tissues; also, we provide information about how systemic metabolism or its metabolites influence epigenetic modifications in the skeletal muscle.

scholarly journals Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1016 ◽  
Author(s):  
Claudia Dompe ◽  
Krzysztof Janowicz ◽  
Greg Hutchings ◽  
Lisa Moncrieff ◽  
Maurycy Jankowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cancer Therapy ◽  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Transcriptional Level ◽  
Cancer Therapies ◽  
Stem Cell Engineering ◽  
Anti Cancer

The epigenome denotes all the information related to gene expression that is not contained in the DNA sequence but rather results from chemical changes to histones and DNA. Epigenetic modifications act in a cooperative way towards the regulation of gene expression, working at the transcriptional or post-transcriptional level, and play a key role in the determination of phenotypic variations in cells containing the same genotype. Epigenetic modifications are important considerations in relation to anti-cancer therapy and regenerative/reconstructive medicine. Moreover, a range of clinical trials have been performed, exploiting the potential of epigenetics in stem cell engineering towards application in disease treatments and diagnostics. Epigenetic studies will most likely be the basis of future cancer therapies, as epigenetic modifications play major roles in tumour formation, malignancy and metastasis. In fact, a large number of currently designed or tested clinical approaches, based on compounds regulating epigenetic pathways in various types of tumours, employ these mechanisms in stem cell bioengineering.

scholarly journals Clinicians’ Expectations for Gene-Driven Cancer Therapy

2014 ◽  
Vol 8 ◽  
pp. CMO.S20737 ◽  
Author(s):  
Antti Jekunen
Keyword(s):  
Decision Making ◽  
Cell Growth ◽  
Cancer Therapy ◽  
Cancer Biology ◽  
Medical Decision Making ◽  
Medical Decision ◽  
Signal Pathways ◽  
New Era ◽  
Therapy Options ◽  
Practicing Physicians

A new era of medicine is rapidly approaching, which will change not only pathological diagnosis but also medical decision-making. This paper raises the question of how well prepared doctors are to address the new issues that will soon confront them. The human genome has been completely sequenced and general understanding about cancer biology has increased enormously with understanding that unregulated gene function and complicated changes in signal pathways are related to uncontrolled cell growth. Thus, gene-driven therapy involving alterations to genes are recognized to present new therapy options. This advance will necessitate major changes to the decision-making aspect of physicians. This article focuses on defining the pertinent changes and addressing what they mean for practicing physicians.

scholarly journals Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?

2018 ◽  
Vol 20 (1) ◽  
pp. 24 ◽  
Author(s):  
Florian Wirsdörfer ◽  
Simone de Leve ◽  
Verena Jendrossek
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Radiation Treatment ◽  
Current Knowledge ◽  
Immune Checkpoint Blockade ◽  
Normal Tissue Toxicity

In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level. Nevertheless, successful cancer therapy remains a major challenge, particularly in tumors with either pronounced resistance to chemotherapy and radiation treatment, a high risk of normal tissue complications, or both, as in lung cancer. Chemotherapy, radiotherapy and immunotherapy have the capacity to evoke adverse effects in normal tissues when administered alone. However, therapy concepts are usually highly complex, and it is still not clear if combining immunotherapy with radio(chemo)therapy will increase the risk of normal tissue complications, in particular since normal tissue toxicity induced by chemotherapy and radiotherapy can involve immunologic processes. Unfortunately, no reliable biomarkers are available so far that are suited to predict the unique normal tissue sensitivity of a given patient to a given treatment. Consequently, clinical trials combining radiotherapy and immunotherapy are attracting major attention, not only regarding efficacy, but also with regard to safety. In the present review, we summarize the current knowledge of radiation-induced and immunotherapy-induced effects in tumor and normal tissue of the lung, and discuss the potential limitations of combined radio-immunotherapy in lung cancer with a focus on the suspected risk for enhanced acute and chronic normal tissue toxicity.

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