Epigenetic mechanisms of bronchopulmonary dysplasia: a review / 中华围产医学杂志

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory complication in preterm infants without fully understand the mechanism or effective treatment,which could significantly affect the survival rate and prognosis of these infants.Studies have confirmed that epigenetic mechanisms,including histone modification,non-coding RNA and DNA methylation may play an essential role in the onset and development of BPD.And most related epigenetic changes are reversible,which might serve as a potential target for BPD treatment.Therefore,further studies on epigenetics will shed light on a better understanding of the pathogenesis,prevention,and treatment of BPD.

Epigenetic mechanisms of bronchopulmonary dysplasia: a review / 中华围产医学杂志

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory complication in preterm infants without fully understand the mechanism or effective treatment, which could significantly affect the survival rate and prognosis of these infants. Studies have confirmed that epigenetic mechanisms, including histone modification, non-coding RNA and DNA methylation may play an essential role in the onset and development of BPD. And most related epigenetic changes are reversible, which might serve as a potential target for BPD treatment. Therefore, further studies on epigenetics will shed light on a better understanding of the pathogenesis, prevention, and treatment of BPD.

Acute pancreatitis and epigenetic regulation mechanisms / 临床肝胆病杂志

Acute pancreatitis is a local pancreatic and systemic inflammatory disease due to various living and environmental factors, such as alcohol, gallstones, high lipids, and smoking, and its pathogenesis remains unclear. Studies have shown that epigenetic regulation mechanisms, such as DNA methylation, histone modification, and non-coding RNA, play an important role in the development and progression of acute pancreatitis. This article introduces the association between the common causes of acute pancreatitis (including alcohol, gallstones, high lipids, and smoking) and epigenetic regulation mechanisms, as well as the association between inflammatory response and epigenetic regulation mechanisms. The preliminary exploration of epigenetic regulation mechanisms in acute pancreatitis provides new thoughts for further understanding the development, progression, and treatment of acute pancreatitis.

The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge / 한국유방암학회지

Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies–the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis–DNA methylation, histone modifications, and noncoding RNAs–advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.

Histone Deacetylase-3 Modification of MicroRNA-31 Promotes Cell Proliferation and Aerobic Glycolysis in Breast Cancer and Is Predictive of Poor Prognosis / 한국유방암학회지

PURPOSE: The incidence and mortality of breast cancer is increasing worldwide. There is a constant quest to understand the underlying molecular biology of breast cancer so as to plan better treatment options. The purpose of the current study was to characterize the expression of histone deacetylases-3 (HDAC3), a member of class I HDACs, and assess the clinical significance of HDAC3 in breast cancer. METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry, and western blot analysis were used to examine messenger RNA and protein expression levels. The relationships between HDAC3 expression and clinicopathological variables were analyzed. MTT assays were used to detect cell proliferation. Glucose-uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were employed to detect aerobic glycolysis. Chromatin immunoprecipitation was used to detect microRNA-31 (miR-31) promoter binding. RESULTS: Our data revealed that HDAC3 was upregulated in breast cancer tissue compared with matched para-carcinoma tissues, and high levels of HDAC3 were positively correlated with advanced TNM stage and N stage of cancer. Furthermore, overexpression of HDAC3 promoted breast cancer cell-proliferation and aerobic glycolysis. The functional involvement of HDAC3 was related in part to the repression of miR-31 transcription via decreased histone H3 acetylation at lysine K9 levels of the miR-31 promoter. Survival analysis revealed that the level of HDAC3 was an independent prognostic factor for breast cancer patients. CONCLUSION: Our findings revealed that HDAC3 served as an oncogene that could promote cell proliferation and aerobic glycolysis and was predictive of a poor prognosis in breast cancer. HDAC3 participated in the cell proliferation of breast cancer, which may prove to be a pivotal epigenetic target against this devastating disease.

Epigenetic regulation of epithelial-mesenchymal transition / 国际肿瘤学杂志

The hallmark of epithelial-mesenchymal transition (EMT) is the loss of E-cadherin.The downregulation of E-cadherin can be mediated by its transcriptional repression through the binding of EMT transcription factors to the E-cadherin promoter.Epigenetic mechanisms including DNA methylation,histone code and microRNAs are involved in the regulation of EMT-related genes.Studies have shown that EMT transcription factors can cooperate with several epigenetic modifiers to participate in the expression of E-cadherin.Targeting epigenetic regulation of EMT represents a new promising therapeutic direction.

Epigenetics: A key paradigm in reproductive health / 대한생식의학회지

It is well established that there is a heritable element of susceptibility to chronic human ailments, yet there is compelling evidence that some components of such heritability are transmitted through non-genetic factors. Due to the complexity of reproductive processes, identifying the inheritance patterns of these factors is not easy. But little doubt exists that besides the genomic backbone, a range of epigenetic cues affect our genetic programme. The inter-generational transmission of epigenetic marks is believed to operate via four principal means that dramatically differ in their information content: DNA methylation, histone modifications, microRNAs and nucleosome positioning. These epigenetic signatures influence the cellular machinery through positive and negative feedback mechanisms either alone or interactively. Understanding how these mechanisms work to activate or deactivate parts of our genetic programme not only on a day-to-day basis but also over generations is an important area of reproductive health research.

Research progress in epigenetic regulation of myocardial ischemia/reperfusion injury by traditional Chinese medicine / 药学学报

Epigenetic is a hotspot of post-genomic era research, and epigenetic modification is a mechanism in the study of cardiovascular disease. Myocardial ischemia-reperfusion injury (MIRI) is one of the problems in the cardiovascular disease, and many experimental interventions are reported in the protection of the ischemic myocardium in experimental animals. However, with the exception of early reperfusion, none has been translated into clinical practice. There is an advantage of traditional Chinese medicine (TCM) in the regulation of epigenetic modification, and pathogenesis of myocardial ischemia-reperfusion injury. This review article is prepared to cover the research progress in the treatment of myocardial ischemia-reperfusion injury by TCM with a focus on epigenetic regulation. The epigenetic regulation is documented in TCM theory through a systematic review of the protecting drugs in the MIRI development guidelines.

Research progress on relationship between histone code and glio-blastoma / 中国肿瘤临床

Histone codes are characterized by the type, location, and modification of amino acids in proteins. Recent research has shown that histone codes are closely related to glioblastoma (GBM). In GBM cells, the combined effects of various effector proteins and histone-modified target sites control the state of chromatins, which further affects the epigenetic phenomena, including GBM cell DNA replication and gene expression and regulation. GBM histone code information exists in histone acetylation, methylation, phos-phorylation, ubiquitination, and other post-translational modification processes. Briefly, this study on the relationship between histone code and GBM provides further molecular targets to develop the clinical diagnosis and treatment of GBM.

Influence of Polycomb Proteins and Epigenetic Transcriptional Modifiers on the Development and Activation of T Lymphocytes / 한양의대학술지

Transcriptional regulation of a gene is not always correlated with genetic information inherited from parents because the transcription of specific genes is often governed by the modification of chromatin structure. The study of transcriptional regulation by modifying chromatin structure is well-known as "epigenetics". Several methods involved in the modification of chromatin structure have been developed in the mammalian species during evolution. Among those methods, methylations of specific DNA region or histone are often used to control specific gene transcription. Therefore, understanding the activity of proteins involved in DNA or histone methylation is an initial step to control the transcriptional activity of a specific gene. Polycomb group (PcG) proteins were known to be repressors of transcription of a specific gene by creating and maintaining methylation or ubiquitination of the specific region of histone. Dependent on the target histone, the activity of PcG proteins effects on the development of specific lineage cells or the activity of specific cell types. In this review, the function, expression and activity of PcG proteins related with the development or activation of T cells are discussed.

Epigenetic Modification in Systemic Rheumatic Diseases

Epigenetics is defined as an inheritable effect that influences gene activity, but does not involve a change in DNA sequence. Epigenetic gene regulation has an essential role in determining individual gene function and activity in each specific cell type. Epigenetics includes four predominant mechanisms: DNA methylation, histone modification, nucleosome positioning and microRNA (miRNA). These mechanisms influence gene expression, cell differentiation, proliferation, DNA repair and replication. Epigenetic modifications are far more sensitive to environmental stimuli than DNA sequence alterations. Candidate gene approaches have identified a small set of genes that undergo epigenetic changes, such as aberrant DNA demethylation, histone modification, as well as regulation by miRNA in rheumatic diseases. It is well known that T cells from patients with SLE or RA, as well as synovial fibroblasts from individuals with RA, have sequences undergoing DNA hypomethylation and/or histone modifications. In addition, miRNA regulates the gene expression by pairing with its target mRNAs and is often deregulated in systemic rheumatic diseases. High-throughput approaches are necessary for screening the epigenetic alterations, and it is essential to screen the specific tissue and cell types that are relevant to the disease pathogenesis. Identification of cell-specific targets of the epigenetic deregulation in rheumatic disorders will provide clinical markers for the diagnosis, disease progression and response to therapy. Our understanding of epigenetics is in its infancy. New generation of pharmaceuticals, which manipulate the epigenome to the switch targeted genes on or off are under investigation. The new field of repairing or optimizing the epigenome through epigenetic modifier and/or diet is wide open.

Epigenetic biomarkers: a step forward for understanding periodontitis

Periodontitis is a common oral disease that is characterized by infection and inflammation of the tooth supporting tissues. While its incidence is highly associated with outgrowth of the pathogenic microbiome, some patients show signs of predisposition and quickly fall into recurrence after treatment. Recent research using genetic associations of candidates as well as genome-wide analysis highlights that variations in genes related to the inflammatory response are associated with an increased risk of periodontitis. Intriguingly, some of the genes are regulated by epigenetic modifications, supposedly established and reprogrammed in response to environmental stimuli. In addition, the treatment with epigenetic drugs improves treatment of periodontitis in a mouse model. In this review, we highlight some of the recent progress identifying genetic factors associated with periodontitis and point to promising approaches in epigenetic research that may contribute to the understanding of molecular mechanisms involving different responses in individuals and the early detection of predispositions that may guide in future oral treatment and disease prevention.

Epigenetic regulation and gastric cancer / 国际肿瘤学杂志

The initiation and development of gastric cancer is due to the effects from both external and internal factors.Recent researches show that external environment factors regulate and control the key genes expression during the process of cell's growth and development through epigenetic modification such as DNA methylation or demethylation,histone modification and small RNA,thus playing an important role in gastric cancer's occurrence and development.

Integrative epigenomic and genomic analysis of malignant pheochromocytoma

Epigenomic and genomic changes affect gene expression and contribute to tumor development. The histone modifications trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) are epigenetic regulators associated to active and silenced genes, respectively and alterations of these modifications have been observed in cancer. Furthermore, genomic aberrations such as DNA copy number changes are common events in tumors. Pheochromocytoma is a rare endocrine tumor of the adrenal gland that mostly occurs sporadic with unknown epigenetic/genetic cause. The majority of cases are benign. Here we aimed to combine the genome-wide profiling of H3K4me3 and H3K27me3, obtained by the ChIP-chip methodology, and DNA copy number data with global gene expression examination in a malignant pheochromocytoma sample. The integrated analysis of the tumor expression levels, in relation to normal adrenal medulla, indicated that either histone modifications or chromosomal alterations, or both, have great impact on the expression of a substantial fraction of the genes in the investigated sample. Candidate tumor suppressor genes identified with decreased expression, a H3K27me3 mark and/or in regions of deletion were for instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9, PTPRE and CDH11. More genes were found with increased expression, a H3K4me3 mark, and/or in regions of gain. Potential oncogenes detected among those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1, IGF2, and the H3K27 trimethylase gene EZH2. Our approach to associate histone methylations and DNA copy number changes to gene expression revealed apparent impact on global gene transcription, and enabled the identification of candidate tumor genes for further exploration.

The Regulation of Histone Modifications / 生物化学与生物物理进展

Epigenetics refers to non-coding sequence changes such as DNA methylation, histone modifications, chromosome remodeling and non-coding RNA regulation.Histone modifications include acetylation, phosphorylation, methylation, ubiquitination and ADP ribosylation.The combinations of different histone modifications, known as "histone code", are dynamic during development and differentiation and play important roles in the regulation of gene expressions in spatial-temporal manners.The modification on a particular residue in a histone affects not only the modifications at different residues in its own protein but also other histones.The histone modifications is a complicated network and the regulation remains elusive.

The PHD Finger:a Reader of The Histone Code / 生物化学与生物物理进展

The PHD finger is a Zn-binding domain found in all eukaryotic genomes, and typically show a C4HC3 signature. Notably, many if not all PHD fingers are found in nuclear proteins whose functions are associated with the regulation of transcription, cell cycle and apoptosis. Increasingly evidences suggest that the PHD finger has multiple functions, including the protein-protein interaction, especially interact with nucleosomes. The pattern and combination of histone modifications, for example, methylation, acetylation, phosphorylation and ubiquitination etc, have been believed to be an important regulator of gene expression and state of the chromatin, which have raised the histone code hypothesis. With the feature of specific recognizing methylated histone, the PHD finger may functions as an important reader of the histone code.

Cancer Epigenetics / 대한소화기학회지

Knowledge regarding molecular events of cancer development has been rapidly accumulated during the last decade. The discovery of tumor suppressor gene-silencing by aberrant promoter CpG island hypermethylation and histone-directed chromatin remodeling has led epigenetics to its recognition as an important alternative mechanism for carcinogenesis. Epigenetics does not involve changes in nucleotide sequences, but it affects on genetic composition in many ways. Cancer cells integratively co-opt genetic and epigenetic mechanisms to acquire different aspects of carcinogenetic phenotypes. Since epigenetic changes can be reversed with relative ease, the research of cancer epigenetics provides great potential for new therapeutic regimens.