DNA甲基化与肝癌

表观遗传学是指非遗传改变(DNA甲基化、组蛋白修饰以及miRNA等非编码RNA)对基因表达调控,这种调节不依赖基因序列的改变且可遗传,其中DNA甲基化是最常见的表观遗传现象。研究表明,在肝癌的发展过程中,表观遗传学改变起到了重要的作用,探讨DNA甲基化的致癌机制可为肿瘤诊治提供理论依据,同时也可作为生物标志物用于肿瘤早期诊断和预后评估。为此,将对肝癌中DNA甲基化改变的特征及其临床应用价值进行阐述。     

组蛋白修饰对炎症反应的调控

表观遗传学（epigenetics）是指在基因的DNA序列不发生改变的情况下,基因的表达水平与功能发生改变,并产生可遗传表型的遗传现象。表观遗传学的研究内容主要包括DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA调控等。     

前列腺癌的表观遗传学研究进展

前列腺癌是男性最常见的恶性肿瘤之一,其病因和发病机制尚不清楚。表观遗传参与了前列腺癌病程的各个阶段,与前列腺癌的发生、发展及转移密切相关,其中DNA甲基化和组蛋白修饰是前列腺癌中最为重要的两种表观遗传表现形式。DNA异常甲基化对肿瘤发生影响机制主要有:基因组广泛性低甲基化、局部过度甲基化、基因突变热点,与前列腺癌DNA损伤修复、激素应答、肿瘤细胞浸润/转移、细胞周期调控等过程密切相关。而组蛋白修饰的异常则将引起相应染色体结构和基因转录水平改变,影响细胞周期、分化和凋亡,导致前列腺癌的发生。目前已有一些针对前列腺癌表观遗传改变的治疗,主要有DNA甲基化转移酶和组蛋白去乙酰化酶抑制剂,并取得了一定的效果。相信随着对表观遗传学研究的深入,必将为前列腺癌的治疗开辟一条新思路。     

DNA甲基化与胆囊癌

DNA甲基化是真核生物的正常修饰方式,异常的DNA甲基化与肿瘤的发生发展密切相关,具有重要生物学意义.胆囊癌中肿瘤相关基因启动子的异常甲基化,作为表观遗传标记物,在胆囊癌的发病、诊治、疗效观察及预后判断等方面可能发挥重要作用.     

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。     

由“肾藏精主骨”理论探讨DNA甲基化修饰与骨质疏松症

骨质疏松症（osteoporosis，OP）是一种以骨结构退化和骨量减少为主要特征的代谢性疾病。《黄帝内经》中提出“肾藏精主骨”理论，将“肾”与“骨”之间的生理病理转化密切联系起来。近年来，随着中国传统医学与表观遗传学研究的发展，甲基化修饰在骨质疏松症发生发展中的作用已成为研究热点。中医药治疗骨质疏松症在分子水平上被证实与DNA甲基化的调控有关，本文基于中医“肾藏精主骨”理论探讨DNA甲基化对骨质疏松症的调控机制，分析DNA甲基化修饰与中医基础理论的有机结合，旨在为中医药现代化研究提供新的参考。     

表观遗传学在骨性关节炎研究中的进展

骨性关节炎(osteoarthritis,OA)是一种最常见的以关节软骨退变为主要病理改变的年龄相关性退化疾病,可表现为不同程度的关节软骨丢失、骨质增生、软骨下骨改变和滑膜炎等.近年来越来越多的证据表明表观遗传修饰在OA发生发展中扮演着非常重要的作用.表观遗传学研究与DNA序列无关的基因表达调控,包括DNA甲基化、组蛋白修饰、miRNA、基因印记等.表观遗传调控可以作为研究OA发病机制的一个新思路.本文就表观遗传学与OA的相关性做一综述.     

表观遗传学与皮肤肿瘤

表观遗传学（Epigenetics）主要研究DNA序列不发生变化时,基因表达异常的机制,以及这种改变又是如何在有丝分裂和减数分裂过程中遗传给后代。表观遗传学机制主要涉及DNA甲基化（DNA methylation）、组蛋白修饰（Histone modification）和microRNA调控（MicroRNA interference）[1]。     

间充质干细胞成软骨分化的表观遗传学研究

表观遗传学机制包括DNA甲基化,组蛋白修饰和microRNA,表观遗传学调控基因表达改变持久、可遗传并且不涉及DNA序列改变,各个领域中对于表观遗传学机制的研究和应用已经成为新的热点。软骨组织再生医学领域中的表观遗传学机制研究,为干细胞向软骨细胞分化以及软骨细胞终末分化提供了多种调控方式。但是,目前的研究主要是在体外常氧条件下,软骨组织工程细胞最终将应用于体内低氧环境中,低氧环境与表观遗传学机制之间相互影响将是研究者们需要关注的重点。本综述意在收集近年来干细胞成软骨分化中表观遗传学调控的研究成果以及各个研究领域中低氧环境与表观遗传学机制间的相互影响,希望能够为软骨组织工程细胞体内应用研究提供新的思路。     

骨质疏松症与表观遗传学

骨质疏松症是老年人常见的退行性疾病,老龄化的社会结构也使得骨质疏松症具有广泛的发病人群,其继发骨折的风险较高,危害性大。骨质疏松症以骨强度下降,骨折风险增加为特征的一种全身性骨骼系统疾病,它受年龄、性别、体内性激素水平、遗传、环境等多方面因素的影响。近年来,随着基因技术的发展,遗传因素与骨质疏松症的相关研究也逐渐增加,其热点之一为表观遗传学。表观遗传是不同于传统孟德尔遗传定律,不通过改变DNA序列所致的可遗传的基因表达变化,它包括DNA甲基化、组蛋白修饰、微小RNA(miRNA)、染色质重塑等。本文就骨质疏松症与表观遗传学的研究现状进行阐述,旨在揭示骨质疏松症在表观遗传学方面可能的发病机制。     

Impact of cigarette‐smoking on sperm DNA methylation and its effect on sperm parameters

DNA methylation is an epigenetic modification of the genome. The purpose of this study was to determine the influence of cigarette‐smoking on sperm DNA methylation from a genomewide survey of sperm samples and to ascertain its effect on sperm parameters. Twenty‐eight sperm DNA samples (from 14 fertile smokers as a case study and 14 proven fertile nonsmokers as controls) were subjected to Infinium 450K BeadChip arrays to identify the changes in the DNA methylation level between the two groups. Then, deep bisulphite sequencing was used to validate five CpGs on 78 samples. The results from the Infinium 450K found that only 11 CpGs showed a significant difference in DNA methylation between the case and the control groups. Five CpGs of the eleven (cg00648582, cg0932376, cg19169023, cg23841288 and cg27391564) underwent deep bisulphite sequencing where cg00648582, related to the PGAM5 gene, and the cg23841288 CpGs, related to the PTPRN2 gene amplicons, showed a significant increase in their DNA methylation level in more than one CpG in the case group. In contrast, a significant decrease was found at cg19169023 and at its various neighbouring CpGs in the TYRO3 gene‐related amplicons. Furthermore, this study demonstrated a significant correlation between the variation in sperm DNA methylation level and standard sperm parameters in the case group.     

DNA methylation level of spermatozoa from subfertile and proven fertile and its relation to standard sperm parameters

The epigenetic mechanism plays an important role in spermatogenesis such as DNA methylation where this episode is represented by either switching genes on or off. Twenty‐eight samples (14 case and 14 controls) were subjected to Infinium 450K BeadChip arrays to identify genomic regions that differ in sperm DNA methylation patterns in the subfertile compared to the proven fertile group. Then two CpGs were validated by deep bisulphite sequencing on 82 sperm samples. The results screening study revealed eight CpGs were significantly different in their sperm DNA methylation levels between cases and control group. The results of the validation study for the two CpGs (cg19779893 and cg19406113) showed that a significant variation in the methylation level at 2 CpGs of 3 CpGs related to cg19779893 site amplicon in cases compared to the controls. Moreover, six CpGs related to the cg19406113 site amplicon showed significant differences in sperm DNA methylation between the cases and the control group. Furthermore, there was a significant decrease in the sperm parameters in the cases compared to the control group. This study found two CpGs altered in their sperm DNA methylation levels. In addition, a strong association was found between changes in the sperm DNA methylation levels in these CpGs sites and sperm parameters.     

DNA甲基化与肝细胞癌

肝细胞癌是原发性肝癌的主要类型,也是常见的恶性肿瘤之一,具有较高的发病率和病死率。然而在分子和细胞水平,肝癌的发病机制仍然不清楚。一般来说,肿瘤形成通常被认为是抑癌基因失活或原癌基因激活致DNA突变而诱导人类正常细胞向恶性细胞转化的过程。近年来随着对肿瘤研究的不断深入,人们发现表观遗传学改变与肝癌发生发展密切相关。其中DNA甲基化是人类基因组发生最为常见的一种表观遗传学事件,也是表观遗传学研究最为深入的一种机制。本文将就DNA甲基化在肝癌中的研究进展作一综述。     

Effects of bariatric surgery on DNA methylation in adults: a systematic review and meta-analysis

BackgroundDNA methylation is an epigenetic mechanism through which environmental factors, including obesity, influence health. Obesity is a major modifiable risk factor for many common diseases, including cardiovascular diseases and cancer. Obesity-induced metabolic stress and inflammation are key mechanisms that affect disease risk and that may result from changes in methylation of metabolic and inflammatory genes.ObjectivesThis review aims to report the effects of weight loss induced by bariatric surgery (BS) on DNA methylation in adults with obesity focusing on changes in metabolic and inflammatory genes.MethodsA systematic review was performed using MEDLINE, EMBASE, and Scopus, to identify studies in adult humans that reported DNA methylation after BS.ResultsOf 15,996 screened titles, 15 intervention studies were identified, all of which reported significantly lower body mass index postsurgery. DNA methylation was assessed in 5 different tissues (blood = 7 studies, adipose tissues = 4, skeletal muscle = 2, liver, and spermatozoa). Twelve studies reported significant changes in DNA methylation after BS. Meta-analysis showed that BS increased methylation of PDK4 loci in skeletal muscle and blood in 2 studies, while the effects of BS on IL6 methylation levels in blood were inconsistent. BS had no overall effect on LINE1 or PPARGC1 methylation.ConclusionThe current evidence supports the reversibility of DNA methylation at specific loci in response to BS-induced weight loss. These changes are consistent with improved metabolic and inflammatory profiles of patients after BS. However, the evidence regarding the effects of BS on DNA methylation in humans is limited and inconsistent, which makes it difficult to combine and compare data across studies.     

精子发生过程中的表观遗传学调控

精子发生是由精原细胞增殖、精母细胞减数分裂以及精子形成所组成的连续过程。精子发生也是染色质不断凝集的过程,最终在精子头部达到高度浓缩状态。近年来的研究表明,表观遗传调控在精子发生过程中发挥作用。我们将从三方面简要阐述精子发生过程中的表观遗传学调控机制:DNA甲基化,组蛋白修饰以及非编码RNA。这些表观因素之间也可以互相调控,通过调控基因表达、转座子活化、性染色体失活以及基因印记等,在精子发生,受精以及胚胎发育过程中扮演重要角色。     

Sperm DNA fragmentation affects epigenetic feature in human male pronucleus

To evaluate whether the sperm DNA fragmentation affects male pronucleus epigenetic factors, semen analysis was performed and DNA fragmentation was assessed by the method of sperm chromatin structure assay (SCSA). Human‐mouse interspecies fertilisation was used to create human male pronucleus. Male pronucleus DNA methylation and H4K12 acetylation were evaluated by immunostaining. Results showed a significant positive correlation between the level of sperm DNA fragmentation and DNA methylation in male pronuclei. In other words, an increase in DNA damage caused an upsurge in DNA methylation. In the case of H4K12 acetylation, no correlation was detected between DNA damage and the level of histone acetylation in the normal group, but results for the group in which male pronuclei were derived from sperm cells with DNA fragmentation, increased DNA damage led to a decreased acetylation level. Sperm DNA fragmentation interferes with the active demethylation process and disrupts the insertion of histones into the male chromatin in the male pronucleus, following fertilisation.     

The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia

PURPOSE: Prostate cancer research has focused significant attention on the mutation, deletion or amplification of the DNA base sequence that encodes critical growth or suppressor genes. However, these changes have left significant gaps in our understanding of the development and progression of disease. It has become clear that epigenetic changes or modifications that influence phenotype without altering the genotype present a new and entirely different mechanism for gene regulation. Several interrelated epigenetic modifications that are altered in abnormal growth states are DNA methylation changes, histone modifications and genomic imprinting. We discuss the status of epigenetic alterations in prostate cancer and benign prostatic hyperplasia progression. In addition, the rationale and status of ongoing clinical trials altering epigenetic processes in urological diseases are reviewed. MATERIALS AND METHODS: An online search of current and past peer reviewed literature on DNA methylation, histone acetylation and methylation, imprinting and epigenetics in prostate cancer and benign prostatic hyperplasia was performed. Relevant articles and reviews were examined and a synopsis of reproducible data was generated with the goal of informing the practicing urologist of these advances and their implications. RESULTS: Only 20 years ago the first study was published demonstrating global changes in DNA methylation patterns in tumors. Accumulating data have now identified specific genes that are commonly hypermethylated and inactivated during prostate cancer progression, including GSTpi, APC, MDR1, GPX3 and 14-3-3sigma. Altered histone modifications, including acetylation and methylation, were also recently described that may modify gene function, including androgen receptor function. These epigenetic changes are now being used to assist in prostate cancer diagnosis and cancer outcome prediction. Epigenetic changes appear to have a role in benign prostatic hyperplasia development as well as in the susceptibility of the prostate to developing cancer. Treatments involving 5-aza-deoxycytosine and other, more selective DNA methyltransferase inhibitors remove methyl residues from silenced genes, generating re-expression, and are currently being used in therapeutic trials. Histone deacetylase inhibitors have shown promise, not only by directly reactivating silenced genes, but also as regulators of apoptosis and sensitizers to radiation therapy. CONCLUSIONS: Evolving data support a significant role for epigenetic processes in the development of prostate cancer and benign prostatic hyperplasia. Epigenetic changes can predict tumor behavior and often distinguish between genetically identical tumors. Targeted drugs that alter epigenetic modifications hold promise as a tool for curing and preventing these diseases.     

血管疾病的表观遗传学研究进展

表观遗传学指独立于DNA核苷酸序列本身的基因表达的可遗传改变,其主要机制包括DNA甲基化、组蛋白修饰和非编码RNA等,这些机制共同作用调控基因的特异性表达。血管疾病是由环境因素和遗传因素相互作用引发的一种慢性疾病。近年来,越来越多的研究证实表观遗传调节在血管疾病的发生发展中具有重要的作用。本文对表观遗传学在血管疾病中的最新研究进展进行综述。