Specific changes in the expression of imprinted genes in prostate cancer—implications for cancer progression and epigenetic regulation

Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation, enhancer of zeste homologue 2 (EZH2) overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer. DNA methylation, EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes. Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes, expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2). A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms. Instead, selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes, which might function in the prostate to limit cell growth induced via the PI3K/Akt pathway, modulate androgen responses and regulate differentiation. Whereas dysregulation of IGF2 may constitute an early change in prostate carcinogenesis, inactivation of this imprinted gene network is rather associated with cancer progression.     

组蛋白修饰与胃肠道恶性肿瘤的关系

目的探讨组蛋白修饰与胃肠道恶性肿瘤的关系。方法复习组蛋白修饰以及组蛋白修饰与胃肠道恶性肿瘤之间关系的相关文献并进行综述。结果组蛋白的修饰为表遗传改变之一,能导致基因表达的改变,在恶性肿瘤的发生、发展中起重要作用。DNA甲基化与组蛋白修饰间相互作用,形成复杂系统,维持基因沉默。表观遗传修饰具有可逆性,逆转表观遗传修饰,从而改变基因表达状态,可能使恶性肿瘤细胞正常化(称为表观基因治疗)。表观基因治疗对于胃肠道恶性肿瘤的预防和治疗具有广阔的应用前景,但还有许多问题需进一步研究证实。结论组蛋白修饰与胃肠道恶性肿瘤的发生有关,逆转表观遗传修饰导致的基因表达改变对于胃肠道恶性肿瘤的预防和治疗具有重要意义。     

神经病理性疼痛的表观遗传学发展方向

背景 神经病理性疼痛(neuropathic pain,NP)是由神经系统的损害或炎症引起的一种常见而特殊的慢性疼痛,以痛觉过敏、异常痛敏和自发痛为特征.目前发病机制不清,发病率逐年上升,处理非常棘手而且目前的治疗方法疗效不佳,是医学领域的挑战性研究课题. 目的 综述表观遗传学在疼痛中的研究状况. 内容 主要对表观遗传学的基本原理、生物学作用以及表观遗传学在疼痛中的研究进展进行综述. 趋向 表观遗传学在NP中的作用将为人们进一步深入阐明疼痛机制提供新的思路,为NP的治疗提供新的策略.     

乳腺癌基因甲基化的研究进展

乳腺癌的发生的分子机制仍然不明确。研究显示表观遗传学改变（Epigenetics）所导致的基因表达异常也是乳腺癌发生、发展的重要原因。表观遗传学改变是基因的核苷酸序列不发生改变的情况下基因表达的可遗传的变化,包括DNA甲基化、组蛋白乙酰化、染色质重塑、基因组印记以及非编码RNA等。乳腺腺的DNA甲基化是常见的分子事件,具有独特的DNA甲基化特征,既往的研究发现DNA甲基化可以作为乳腺癌早期诊断、分型、监测药物治疗效果和预后的分子标志物。本文将对DNA甲基化在乳腺癌的研究进展进行综述。     

Epigenetics in prostate cancer: biologic and clinical relevance

Context

Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence.

Objective

To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge.

Evidence acquisition

PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications.

Evidence synthesis

Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance.

Conclusions

Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic.     

A review of the alterations in DNA methylation in esophageal squamous cell carcinoma

Epigenetic changes such as DNA methylation, histone modification, and loss of genome imprinting play a crucial role in esophageal squamous cell carcinogenesis, along with genomic and genetic alterations. DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of alterations of DNA methylation: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. In several types of human cancers, the methods of detecting an aberrant methylation status have been applied to clinical fields to stratify high-risk groups, detect early cancer, and predict clinical outcomes. Importantly, epigenetic changes, including alterations in DNA methylation, are reversible and can thus be targets for cancer therapy or chemoprevention. Therefore, a better understanding of the DNA methylation in esophageal squamous cell carcinoma (ESCC) is important for optimizing cancer therapy and chemoprevention. We herein summarize the current knowledge regarding alterations in DNA methylation and the clinical implications in ESCC.     

A methyl-deficient diet modifies histone methylation and alters Igf2 and H19 repression in the prostate

BACKGROUND: Folate and methyl-group deficiency has been linked to prostate cancer susceptibility, yet the mechanisms underlying these observations are incompletely understood. The region of the genome containing the imprinted genes insulin-like growth factor 2 (Igf2) and H19, both of which display oncogenic functions, may be particularly sensitive to environmental influences. METHODS: To determine whether a methyl-deficient diet impacts epigenetic controls at the Igf2-H19 locus, we placed C57BL/6 mice containing a polymorphism at the imprinted Igf2-H19 locus on a choline and methionine deficient (CMD) diet. We interrogated this locus for expression and epigenetic changes in prostate tissues. RESULTS: A significant increase in both Igf2 and H19 expression was found in CMD prostate tissues compared to controls. These expression changes were reversible with shorter exposure to the CMD diet. Chromatin immunoprecipitation (ChIP) revealed significant decreases in repressive histone modifications (dimethyl-H3K9) within the H19 promoter, as well as Igf2 P2 and P3 promoters. DNA methylation within these promoters was not altered. No significant change in Igf2 or H19 imprinting was observed. CONCLUSIONS: These findings highlight the plasticity of the epigenome in an epithelial organ vulnerable to neoplastic change. They further suggest that chromatin modifications are more susceptible to methyl-deficient diets than DNA methylation at this locus.     

Epigenetic alterations and their clinical implications in esophageal squamous cell carcinoma

Alterations in the regulation of gene expression that do not involve a change in the DNA sequence have been increasingly recognized as an important key event of carcinogenesis, referred to as “epigenetic” changes. Major epigenetic mechanisms include the methylation of cytosines in DNA, changes of histone and chromatin structure by covalent posttranslational modifications of histone proteins and alterations in the expression of microRNAs. These epigenetic alterations have also been identified in esophageal squamous cell carcinoma (ESCC). In this brief review, we will discuss DNA hypermethylation of the tumor suppressor gene promoters, histone modifications including histone acetylation/deacetylation and histone methylation and microRNAs in ESCC. Clinical implications of these epigenetic alterations in ESCC will be also discussed.     

Epigenetic mechanisms in cartilage and osteoarthritis: DNA methylation, histone modifications and microRNAs

Osteoarthritis (OA) is a complex multifactorial disease with a strong genetic component. Several studies have suggested or identified epigenetic events that may play a role in OA progression and the gene expression changes observed in diseased cartilage. The aim of this review is to inform about current research in epigenetics and epigenetics in OA. Epigenetic mechanisms include DNA methylation, histone modifications, and microRNAs. Collectively, these enable the cell to respond quickly to environmental changes and can be inherited during cell division. However, aberrant epigenetic modifications are associated with a number of pathological conditions, including OA. Advancements in epigenetic research suggests that global analysis of such modifications in OA are now possible, however, with the exception of microRNAs, it will be a significant challenge to demonstrate how such events impact on the disease.     

Epigenetic targets in the diagnosis and treatment of prostate cancer

Prostate cancer (PC) is one of leading cause of cancer related deaths in men. Various aspects of cancer epigenetics are rapidly evolving and the role of 2 major epigenetic changes including DNA methylation and histone modifications in prostate cancer is being studied widely. The epigenetic changes are early event in the cancer development and are reversible. Novel epigenetic markers are being studied, which have the potential as sensitive diagnostic and prognostic marker. Variety of drugs targeting epigenetic changes are being studied, which can be effective individually or in combination with other conventional drugs in PC treatment. In this review, we discuss epigenetic changes associated with PC and their potential diagnostic and therapeutic applications including future areas of research.     

The Role of Histone Modifications and Variants in Regulating Gene Expression in Breast Cancer

The role of epigenetic phenomena in cancer biology is increasingly being recognized. Here we focus on the mechanisms and enzymes involved in regulating histone methylation and acetylation, and the modulation of histone variant expression and deposition. Implications of these epigenetic marks for tumor development, progression and invasiveness are discussed with a particular emphasis on breast cancer progression.     

表观遗传调控在脊柱韧带骨化中的作用研究进展

脊柱韧带骨化以脊柱韧带组织内出现病理性骨组织为特征,好发于颈段和胸段,是造成椎管狭窄的重要病因。骨化块对脊髓或神经根的压迫可导致严重的神经功能障碍,给患者生活质量带来巨大影响。目前脊柱韧带骨化的具体病因及发病机制尚不明确。表观遗传调控在生物体内广泛存在,指在不改变基因组DNA序列的前提下使生物体出现具有可遗传的基因表达...     

DNA甲基化与前列腺癌

DNA甲基化是恶性肿瘤普遍存在的分子生物学改变,与肿瘤的发生和发展密切相关。前列腺癌中存在多种基因的甲基化,涉及到DNA损伤修复、激素应答、肿瘤细胞入侵/转移、细胞周期调控等通路。前列腺癌前病变如前列腺上皮内瘤也存在DNA甲基化,但程度相对较低。DNA甲基化的研究为前列腺癌的早期诊断、预后评估及激素非依赖性前列腺癌的治疗提供了新的途径。