Epigenetic biomarkers in colorectal cancer: premises and prospects

Context: Colorectal cancer is one of the most common cancers worldwide. Epigenetic alterations play an important role in the pathogenesis of the colorectal cancer.

Objective: This review has focused on the most recent investigations, which has suggested potential epigenetic biomarkers in colorectal cancer.

Methods: Evidences were achieved by searching online medical databases including Google scholar, Pubmed, Scopus and Science Direct.

Results: Extensive studies have indicated that aberrant epigenetic modifications could serve as potential biomarkers for diagnosis, prognosis and prediction of colorectal cancer.

Conclusion: Advances in aberrant epigenetic modifications can open new avenues for exploration of reliable and robust biomarkers to improve the management of CRC patients.     

Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives

Non-small cell lung cancer (NSCLC) still constitutes the most common cancer-related cause of death worldwide. All efforts to introduce suitable treatment options using chemotherapeutics or targeted therapies have, up to this point, failed to exhibit a substantial effect on the 5-year-survival rate. The involvement of epigenetic alterations in the evolution of different cancers has led to the development of epigenetics-based therapies, mainly targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes. So far, their greatest success stories have been registered in hematologic neoplasias. As the effects of epigenetic single agent treatment of solid tumors have been limited, the investigative focus now lies on combination therapies of epigenetically active agents with conventional chemotherapy, immunotherapy, or kinase inhibitors. This review includes a short overview of the most important preclinical approaches as well as an extensive discussion of clinical trials using epigenetic combination therapies in NSCLC, including ongoing trials. Thus, we are providing an overview of what lies ahead in the field of epigenetic combinatory therapies of NSCLC in the coming years.     

Hot topics in epigenetic mechanisms of aging: 2011

Aging is a complex process that results in compromised biological functions of the organism and increased susceptibility to disease and death. Although the molecular basis of aging is currently being investigated in many experimental contexts, there is no consensus theory to fully explain the aging process. Epigenetic factors, including DNA methylation, histone modifications, and microRNA expression, may play central roles in controlling changes in gene expression and genomic instability during aging. In this Hot Topic review, we first examine the mechanisms by which these epigenetic factors contribute to aging in diverse eukaryotic species including experimental models of yeasts, worms, and mammals. In a second section, we will emphasize in the mammalian epigenetic alterations and how they may affect human longevity by altering stem cell function and/or somatic cell decline. The field of aging epigenetics is ripe with potential, but is still in its infancy, as new layers of complexity are emerging in the epigenetic network. As an example, we are only beginning to understand the relevance of non-coding genome to organism aging or the existence of an epigenetic memory with transgenerational inheritance. Addressing these topics will be fundamental for exploiting epigenetics phenomena as markers of aging-related diseases or as therapeutic targets.     

表观遗传修饰与肿瘤

肿瘤的形成受遗传学修饰和表观遗传修饰的影响。长期以来人们一直认为基因突变参与肿瘤的形成,近年来越来越多的证据表明,表观遗传修饰在肿瘤进展中同样具有非常重要的作用。表观遗传调控可以影响基因转录活性而不涉及DNA序列的改变。本文介绍了肿瘤发生发展过程中出现的表观遗传修饰异常,以及通过干预表观遗传修饰治疗肿瘤的应用前景。     

German-Catalan workshop on epigenetics and cancer

In the First German-Catalan Workshop on Epigenetics and Cancer held in Heidelberg, Germany (June 17–19, 2013), cutting-edge laboratories (PEBC, IMPPC, DKFZ, and the Collaborative Research Centre Medical Epigenetics of Freiburg) discussed the latest breakthroughs in the field. The importance of DNA demethylation, non-coding and imprinted genes, metabolic stress, and cell transdifferentiation processes in cancer and non-cancer diseases were addressed in several lectures in a very participative and dynamic atmosphere.

The meeting brought together leading figures in the field of cancer epigenetics to present their research work from the last five years. Experts in different areas of oncology described important advances in colorectal, lung, neuroblastoma, leukemia, and lymphoma cancers. The workshop also provided an interesting forum for pediatrics, and focused on the need to improve the treatment of childhood tumors in order to avoid, as far as possible, brain damage and disruption of activity in areas of high plasticity. From the beginning, the relevance of “omics” and the advances in genome-wide analysis platforms, which allow cancer to be studied in a more comprehensive and inclusive way, was very clear. Modern “omics” offer the possibility of identifying metastases of uncertain origin and establishing epigenetic signatures linked to a specific cluster of patients with a particular prognosis. In this context, invited speakers described novel tumor-associated histone variants and DNA-specific methylation, highlighting their close connection with other processes such as cell-lineage commitment and stemness.     

Epigenetic modulation of the immune function

Great efforts in the field of solid organ transplantation are being devoted to identifying biomarkers that allow a transplanted patient’s immune status to be established. Recently, it has been well documented that epigenetic mechanisms like DNA methylation and histone modifications regulate the expression of immune system-related genes, modifying the development of the innate and adaptive immune responses. An in-depth knowledge of these epigenetic mechanisms could modulate the immune response after transplantation and to develop new therapeutic strategies. Epigenetic modifiers, such as histone deacetylase (HDAC) inhibitors have considerable potential as anti-inflammatory and immunosuppressive agents, but their effect on transplantation has not hitherto been known. Moreover, the detection of epigenetic marks in key immune genes could be useful as biomarkers of rejection and progression among transplanted patients. Here, we describe recent discoveries concerning the epigenetic regulation of the immune system, and how this knowledge could be translated to the field of transplantation.     

Histone modifications as a platform for cancer therapy

Tumorigenesis and metastasis are a progression of events resulting from alterations in the processing of the genetic information. These alterations result from stable genetic changes (mutations) involving tumor suppressor genes and oncogenes (e.g., ras, BRAF) and potentially reversible epigenetic changes, which are modifications in gene function without a change in the DNA sequence. Mutations of genes coding for proteins that directly or indirectly influence epigenetic processes will alter the cell's gene expression program. Epigenetic mechanisms often altered in cancer cells are DNA methylation and histone modifications (acetylation, methylation, phosphorylation). This article will review the potential of these reversible epigenetic processes as targets for cancer therapies.     

Epigenetic regulation: methylation of histone and non-histone proteins

Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmitted into daughter cells and through what mechanisms are currently under active investigation. Previously, methylation was considered to be irreversible, but the recent discovery of histone lysine demethylases revealed a dynamic nature of histone methylation regulation on four of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27 and H3K36). Even so, it is still unclear whether demethylases specific for the remaining two sites, H3K79 and H4K20, exist. Furthermore, besides histone proteins, the lysine methylation and demethylation also occur on non-histone proteins, which are probably subjected to similar regulation as histones. This review discusses recent progresses in protein lysine methylation regulation focusing on the above topics, while referring readers to a number of recent reviews for the biochemistry and biology of these enzymes     

Epigenetic regulators and histone modification.

Epigenetic inheritance is a key element in the adaptation of organisms to a rapidly changing environment without stably changing their DNA sequence. The necessary changes in its gene expression profiles are frequently associated with variations in chromatin structure. The conformation of chromatin is profoundly influenced by the post-translational modification of the histone proteins, the incorporation of histone variants, the activity of nucleosome remodelling factors and the association of non-histone chromatin proteins. Although the hierarchy of these factors is still not fully understood, genetic experiments suggest that histone-modifying enzymes play a major causal role in setting up a particular chromatin structure. In this article, the recent progress that was made to understand the molecular mechanisms of the targeting and regulation of histone modifiers and its implication for epigenetic inheritance are reviewed.     

表观遗传学: 生物细胞非编码RNA调控的研究进展

表观遗传学是研究基因表达发生了可遗传的改变, 而DNA序列不发生改变的一门生物学分支, 对细胞的生长分化及肿瘤的发生发展至关重要。表观遗传学的主要机制包括DNA甲基化、组蛋白修饰及新近发现的非编码RNA。非编码RNA 是指不能翻译为蛋白的功能性RNA分子, 其中常见的具调控作用的非编码RNA包括小干涉RNA、miRNA、piRNA 以及长链非编码RNA。近年来大量研究表明非编码RNA在表观遗传学的调控中扮演了越来越重要的角色。文章综述了近年来生物细胞非编码RNA调控的表观遗传学研究进展, 以有助于理解哺乳动物细胞中非编码RNA及其调控机制和功能。     

表观遗传修饰在学习记忆中的研究进展

学习记忆是大脑的重要功能.记忆的形成涉及基因转录、新蛋白质合成和突触可塑性改变等一系列分子和细胞乃至神经环路的变化.近些年研究者逐渐发现各种表观遗传修饰,包括DNA甲基化、组蛋白修饰及RNA修饰在各种学习记忆类型、记忆阶段和突触可塑性中发挥了不同程度的作用.本文阐述了参与学习记忆的不同表观遗传调控因子,为进一步理解学习...     

表观遗传学——耳聋研究的新视野

耳聋是一种常见的人类感觉系统缺陷,新生儿发病率可达1/1000～3/1000。耳蜗感觉神经上皮毛细胞的结构或功能异常可导致耳聋,遗传因素在其中起重要作用。虽然一些与遗传性耳聋相关的基因及染色体位点已经被定位或克隆,仍有很多耳聋的病因尚不清楚。人们发现,除了常见的热点基因突变(GJB2、SLC26A4、线粒体DNA C1494T和A1555G等)外,一些表观遗传学的改变也在耳聋的发生中起重要作用。例如,miR-96突变会导致人和小鼠的渐进性失聪,异常的CpG岛甲基化与一些耳聋综合征的发生有关等。文章着重对表观遗传学在耳聋领域的研究现状和进展进行了综述。