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Studies have shown that alterations of epigenetics and microRNAs (miRNAs) play critical roles in the initiation and progression of human cancer. Epigenetic silencing of tumor suppressor genes in cancer cells is generally mediated by DNA hypermethylation of CpG island promoter and histone modification such as methylation of histone H3 lysine 9 (H3K9) and tri-methylation of H3K27. MiRNAs are small non-coding RNAs that regulate expression of various target genes. Specific miRNAs are aberrantly expressed and play roles as tumor suppressors or oncogenes during carcinogenesis. Important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in activation of target oncogenes in human malignancies. Stem cells have the ability to perpetuate themselves through self-renewal and to generate mature cells of various tissues through differentiation. Accumulating evidence suggests that a subpopulation of cancer cells with distinct stem-like properties is responsible for tumor initiation, invasive growth, and metastasis formation, which is defined as cancer stem cells. Cancer stem cells are considered to be resistant to conventional chemotherapy and radiation therapy, suggesting that these cells are important targets of cancer therapy. DNA methylation, histone modification and miRNAs may be deeply involved in stem-like properties in cancer cells. Restoring the expression of tumor suppressor genes and miRNAs by chromatin modifying drugs may be a promising therapeutic approach for cancer stem cells. In this Research Topic, we discuss about alterations of epigenetics and miRNAs in cancer and cancer stem cell and understand the molecular mechanism underlying the formation of cancer stem cell, which may provide a novel insight for treatment of refractory cancer.

epigenetics --- MicroRNAs --- Cancer --- cancer stem cells --- Methylation

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Symbiosis is an intimate relationship between different living entities and is widespread in virtually all organisms. It was critical for the origin and diversification of Eukaryotes and represents a major driving force in evolution. Indeed, symbiosis may support a wide range of biological processes, including those underlying the physiology, development, reproduction, health, behavior, ecology and evolution of the organisms involved in the relationship. Although often confused with mutualism, when both organisms benefit from the association, symbiosis actually encompasses several and variable relationships. Among them is parasitism, when one organism benefits but the other is harmed, and commensalism, when one organism benefits and the other remains unaffected. Even if many symbiotic lifestyles do exist in nature, in many cases the intimacy between the partners is so deep that the “symbiont” (sensu strictu) resides into the tissues and/or cells of the other partner. Since the partners frequently belong to different kingdoms, e.g. bacteria, fungi, protists and viruses living in association with animal and plant hosts, their shared “language” should be a basic and ancient form of communication able to effectively blur the boundaries between extremely different living entities. In recent years studies on the role of epigenetics in shaping host-symbiont interactions have been flourishing. Epigenetic changes include, but are not limited to, DNA methylation, remodelling of chromatin structure through histone chemical modifications and RNA interference. In this E-book we present a series of papers exploring the fascinating developmental and evolutionary relationship between symbionts and hosts, by focusing on the mediating epigenetic processes that enable the communication to be effective and robust at both the individual, the ecological and the evolutionary time scales. In particular, the papers consider the role of epigenetic factors and mechanisms in the interactions among different species, comprising the holobiont and host-parasite relationships. On the whole, since epigenetics is fast-acting and reversible, enabling dynamic developmental communication between hosts and symbionts at several different time scale, we argue that it could account for the enormous plasticity that characterizes the interactions between all the organisms living symbiotically on our planet.

chromatin re-modeling --- DNA Methylation --- epigenetics --- genome immunity --- Histone Modifications --- holobiont --- host-symbiont crosstalk --- pathogen --- symbiosis

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Alterations in gene expression are essential during growth and development phases and when plants are exposed to environmental challenges. Stress conditions induce gene expression modifications, which are associated with changes in the biochemical and physiological processes that help plants to avoid or reduce potential damage resulting from these stresses.After exposure to stress, surviving plants tend to flower earlier than normal and therefore transfer the accumulated epigenetic information to their progenies, given that seeds, where this information is stored, are formed at a later stage of plant development.DNA methylation is correlated with expression repression. Likewise, miRNA produced in the cell can reduce the transcript abundance or even prevent translation of mRNA. However, histone modulation, such as histone acetylation, methylation, and ubiquitination, can show distinct effects on gene expression. These alterations can be inherited, especially if the plants are consistently exposed to a particular environmental stress. Retrotransposons and retroviruses are foreign movable DNA elements that play an important role in plant evolution. Recent studies have shown that epigenetic alterations control the movement and the expression of genes harbored within these elements. These epigenetic modifications have an impact on the morphology, and biotic and abiotic tolerance in the subsequent generations because they can be inherited through the transgenerational memory in plants. Therefore, epigenetic modifications, including DNA methylation, histone modifications, and small RNA interference, serve not only to alter gene expression but also may enhance the evolutionary process in eukaryotes.In this E-book, original research and review articles that cover issues related to the role of DNA methylation, histone modifications, and small RNA in plant transgenerational epigenetic memory were published.The knowledge published on this topic may add new insight on the involvement of epigenetic factors in natural selection and environmental adaptation. This information may also help to generate a modeling system to study the epigenetic role in evolution.

transgeneration memory --- DNA methylation --- epigenetics --- chromatin --- environmental stresses --- evolution --- histones --- replication

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Epigenetics is defined as the study of modifications of the genome, heritable during cell division that does not involve changes in DNA sequences. Up to date, epigenetic modifications involve at least three general mechanisms regulating gene expression: histone modifications, DNA methylation, and non-coding RNAs (ncRNAs). For the past two decades, an explosion in our interest and understanding of epigenetic mechanisms has been seen. This mainly based on the influence that epigenetic alterations have on an amazing number of biological processes, such as gene expression, imprinting, programmed DNA rearrangements, germ line silencing, developmentally cued stem cell division, and overall chromosomal stability and identity. It has become also evident that the constant exposure of living organisms to environment factors affects their genomes through epigenetic mechanisms. Viruses infecting animal cells are thought to play central roles in shaping the epigenetic scenario of infected cells. In this context it has become obvious that knowing the impact that viral infections have on the epigenetic control of their host cells will certainly lead to a better understanding of the interplay viruses have with animal cells. In fact, DNA viruses use host transcription factors as well as epigenetic regulators in such a way that they affect epigenetic control of gene expression that extends to host gene expression. At the same time, animal cells employ mechanisms controlling transcription factors and epigenetic processes, in order to eliminate viral infections. In summary, epigenetic mechanisms are involved in most virus-cell interactions. We now know that some viruses exhibit epigenetic immune evasion mechanisms to survive and propagate in their host; however, there is still much ambiguity over these epigenetic mechanisms of viral immune evasion, and most of the discovered mechanisms are still incomplete. Other animal viruses associated to cancer often deregulate cellular epigenetic mechanisms, silencing cellular tumor-suppressor genes and/or activating either viral or host cell oncogenes. In addition, in several cancers the down-regulation of tumor suppressor protein-coding genes and ncRNAs with growth inhibitory functions, such as miRNAs, have been closely linked to the presence of cell CpG island promoter hypermethylation. The goal of the aforementioned Research Topic is to bring together the key experimental and theoretical research, linking state-of-the-art knowledge about the epigenetic mechanisms involved in animal virus-cell interactions.

epigenetic --- DNA Methylation --- Interference RNA --- histone modification --- Methyltransferases --- Immune System --- DNase I hypersensitive sites --- virus --- Oncolytic Virotherapy --- NGS technology

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Cancer remains one of the main causes of morbidity and mortality worldwide. Although many pharmacological and clinical advances have been made, there is a constant need for new molecules to improve the overall options for treatment. Natural compounds from animal, microbial, vegetal, or fungal origin represent countless sources of new compounds that can be used as anticancer drugs, provided their activity, bioavailability, and toxicity are adequate. This book aims to compile both original articles and reviews that cover the most recent advances in the use of natural compounds for cancer treatment, and provide new objectives and advice for future research in the field of biological activity of natural compounds.

resveratrol --- miR-663 --- inflammation --- cancer --- cardiovascular disease --- animal model --- treatment --- bladder cancer --- epidemiology --- green tea --- probiotics --- synbiotics --- microbiome --- microbiota --- colorectal cancer --- Momordica cochinchinensis --- Gac --- seeds --- saponins --- trypsin inhibitors --- phenolics --- anticancer --- antioxidant --- extraction --- freeze dried extract --- royal jelly --- adverse events --- tyrosine kinase inhibitors --- renal cell carcinoma --- double-blinded --- randomized clinical trial --- cancer --- natural compound --- synergy --- xenohormesis --- polypharmacology --- resveratrol --- epigenetic --- methylation --- acetylation --- sulforaphane --- epigenetic --- 5-aza-2’-deoxycytine --- melanoma --- n/a