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Inheritance of Stress Responses via Small Non-Coding RNAs in Invertebrates and Mammals 无脊椎动物和哺乳动物通过小非编码 RNA 遗传应激反应
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-12-19 DOI: 10.3390/epigenomes8010001
Maria C. Ow, Sarah E. Hall
While reports on the generational inheritance of a parental response to stress have been widely reported in animals, the molecular mechanisms behind this phenomenon have only recently emerged. The booming interest in epigenetic inheritance has been facilitated in part by the discovery that small non-coding RNAs are one of its principal conduits. Discovered 30 years ago in the Caenorhabditis elegans nematode, these small molecules have since cemented their critical roles in regulating virtually all aspects of eukaryotic development. Here, we provide an overview on the current understanding of epigenetic inheritance in animals, including mice and C. elegans, as it pertains to stresses such as temperature, nutritional, and pathogenic encounters. We focus on C. elegans to address the mechanistic complexity of how small RNAs target their cohort mRNAs to effect gene expression and how they govern the propagation or termination of generational perdurance in epigenetic inheritance. Presently, while a great amount has been learned regarding the heritability of gene expression states, many more questions remain unanswered and warrant further investigation.
虽然有关父母对压力的反应代代相传的报道在动物中广泛存在,但这种现象背后的分子机制直到最近才出现。人们对表观遗传的兴趣日渐浓厚,部分原因是人们发现小的非编码 RNA 是表观遗传的主要渠道之一。30 年前,这些小分子在秀丽隐杆线虫中被发现,此后,它们在调控真核生物发育的几乎所有方面发挥了重要作用。在这里,我们将概述目前对动物(包括小鼠和线虫)表观遗传的理解,因为它与温度、营养和病原体等压力有关。我们以 elegans 为研究对象,探讨小 RNA 如何靶向同源 mRNA 影响基因表达,以及它们如何在表观遗传中控制世代耐久性的传播或终止的复杂机制。目前,虽然已经了解了大量有关基因表达状态遗传性的知识,但还有许多问题尚未得到解答,需要进一步研究。
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引用次数: 0
Epigenetic Mechanisms in Hematologic Aging and Premalignant Conditions. 血液学衰老和恶性肿瘤前病变的表观遗传机制
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-12-12 DOI: 10.3390/epigenomes7040032
Bowen Yan, Qingchen Yuan, Olga A Guryanova

Hematopoietic stem cells (HSCs) are essential for maintaining overall health by continuously generating blood cells throughout an individual's lifespan. However, as individuals age, the hematopoietic system undergoes significant functional decline, rendering them more susceptible to age-related diseases. Growing research evidence has highlighted the critical role of epigenetic regulation in this age-associated decline. This review aims to provide an overview of the diverse epigenetic mechanisms involved in the regulation of normal HSCs during the aging process and their implications in aging-related diseases. Understanding the intricate interplay of epigenetic mechanisms that contribute to aging-related changes in the hematopoietic system holds great potential for the development of innovative strategies to delay the aging process. In fact, interventions targeting epigenetic modifications have shown promising outcomes in alleviating aging-related phenotypes and extending lifespan in various animal models. Small molecule-based therapies and reprogramming strategies enabling epigenetic rejuvenation have emerged as effective approaches for ameliorating or even reversing aging-related conditions. By acquiring a deeper understanding of these epigenetic mechanisms, it is anticipated that interventions can be devised to prevent or mitigate the rates of hematologic aging and associated diseases later in life. Ultimately, these advancements have the potential to improve overall health and enhance the quality of life in aging individuals.

造血干细胞(HSCs)在人的一生中不断生成血细胞,对维持整体健康至关重要。然而,随着年龄的增长,造血系统的功能会显著下降,从而更容易患上与年龄相关的疾病。越来越多的研究证据凸显了表观遗传调控在这种与年龄相关的衰退中的关键作用。本综述旨在概述正常造血干细胞在衰老过程中参与调控的各种表观遗传机制及其对衰老相关疾病的影响。了解导致造血系统衰老相关变化的表观遗传机制之间错综复杂的相互作用,对于开发延缓衰老过程的创新策略具有巨大潜力。事实上,针对表观遗传修饰的干预措施在缓解衰老相关表型和延长各种动物模型的寿命方面已显示出良好的效果。基于小分子的疗法和表观遗传重塑策略已成为改善甚至逆转衰老相关病症的有效方法。通过更深入地了解这些表观遗传机制,预计可以设计出干预措施,预防或减轻血液学衰老及相关疾病的发生率。最终,这些进展有可能改善老龄人的整体健康并提高其生活质量。
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引用次数: 0
World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence 世贸中心暴露、DNA 甲基化变化与癌症:当前证据综述
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-12-08 DOI: 10.3390/epigenomes7040031
S. Tuminello, Emelie Nguyen, N. Durmus, Ramazan Alptekin, Muhammed Yilmaz, Maria Cecilia Crisanti, M. Snuderl, Yu Chen, Yongzhao Shao, Joan Reibman, Emanuela Taioli, Alan A. Arslan
Introduction: Known carcinogens in the dust and fumes from the destruction of the World Trade Center (WTC) towers on 9 November 2001 included metals, asbestos, and organic pollutants, which have been shown to modify epigenetic status. Epigenome-wide association analyses (EWAS) using uniform (Illumina) methodology have identified novel epigenetic profiles of WTC exposure. Methods: We reviewed all published data, comparing differentially methylated gene profiles identified in the prior EWAS studies of WTC exposure. This included DNA methylation changes in blood-derived DNA from cases of cancer-free “Survivors” and those with breast cancer, as well as tissue-derived DNA from “Responders” with prostate cancer. Emerging molecular pathways related to the observed DNA methylation changes in WTC-exposed groups were explored and summarized. Results: WTC dust exposure appears to be associated with DNA methylation changes across the genome. Notably, WTC dust exposure appears to be associated with increased global DNA methylation; direct dysregulation of cancer genes and pathways, including inflammation and immune system dysregulation; and endocrine system disruption, as well as disruption of cholesterol homeostasis and lipid metabolism. Conclusion: WTC dust exposure appears to be associated with biologically meaningful DNA methylation changes, with implications for carcinogenesis and development of other chronic diseases.
导言:2001年11月9日世界贸易中心(WTC)双塔被毁的尘埃和烟雾中已知的致癌物包括金属、石棉和有机污染物,这些物质已被证明可以改变表观遗传状态。使用统一(Illumina)方法的全表观基因组关联分析(EWAS)已经确定了WTC暴露的新表观遗传谱。方法:我们回顾了所有已发表的数据,比较了在WTC暴露的EWAS研究中发现的差异甲基化基因谱。这包括来自无癌症“幸存者”和乳腺癌患者的血液来源DNA的DNA甲基化变化,以及来自前列腺癌“响应者”的组织来源DNA。对wtc暴露组DNA甲基化变化相关的新分子途径进行了探索和总结。结果:WTC粉尘暴露似乎与整个基因组的DNA甲基化变化有关。值得注意的是,WTC粉尘暴露似乎与全球DNA甲基化增加有关;癌症基因和途径的直接失调,包括炎症和免疫系统失调;内分泌系统紊乱,以及胆固醇稳态和脂质代谢紊乱。结论:WTC粉尘暴露似乎与具有生物学意义的DNA甲基化变化有关,对致癌和其他慢性疾病的发展具有影响。
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引用次数: 0
Comparison of Yersinia enterocolitica DNA Methylation at Ambient and Host Temperatures. 环境温度和宿主温度下小肠结肠炎耶尔森菌 DNA 甲基化的比较
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-11-30 DOI: 10.3390/epigenomes7040030
Dustin J Van Hofwegen, Carolyn J Hovde, Scott A Minnich

Pathogenic bacteria recognize environmental cues to vary gene expression for host adaptation. Moving from ambient to host temperature, Yersinia enterocolitica responds by immediately repressing flagella synthesis and inducing the virulence plasmid (pYV)-encoded type III secretion system. In contrast, shifting from host to ambient temperature requires 2.5 generations to restore motility, suggesting a link to the cell cycle. We hypothesized that differential DNA methylation contributes to temperature-regulated gene expression. We tested this hypothesis by comparing single-molecule real-time (SMRT) sequencing of Y. enterocolitica DNA from cells growing exponentially at 22 °C and 37 °C. The inter-pulse duration ratio rather than the traditional QV scoring was the kinetic metric to compare DNA from cells grown at each temperature. All 565 YenI restriction sites were fully methylated at both temperatures. Among the 27,118 DNA adenine methylase (Dam) sites, 42 had differential methylation patterns, while 17 remained unmethylated regardless of the temperature. A subset of the differentially methylated Dam sites localized to promoter regions of predicted regulatory genes including LysR-type and PadR-like transcriptional regulators and a cyclic-di-GMP phosphodiesterase. The unmethylated Dam sites localized with a bias to the replication terminus, suggesting they were protected from Dam methylase. No cytosine methylation was detected at Dcm sites.

致病细菌识别环境线索,改变基因表达以适应宿主。从环境温度到宿主温度,小肠结肠耶尔森菌(Yersinia enterocolitica)的反应是立即抑制鞭毛合成,并诱导毒力质粒(pYV)编码的 III 型分泌系统。相反,从宿主温度转移到环境温度需要 2.5 代才能恢复运动能力,这表明与细胞周期有关。我们假设,不同的 DNA 甲基化有助于温度调节的基因表达。我们通过比较单分子实时(SMRT)测序对在22 °C和37 °C下指数生长的小肠结肠炎病毒细胞DNA进行了测试。脉冲间持续时间比值而非传统的 QV 评分是比较在不同温度下生长的细胞 DNA 的动力学指标。在两种温度下,所有 565 个 YenI 限制位点都完全甲基化。在27118个DNA腺嘌呤甲基化酶(Dam)位点中,42个位点的甲基化模式不同,而17个位点无论温度如何都保持未甲基化。不同甲基化的Dam位点的一部分定位在预测的调控基因的启动子区域,包括LysR型和PadR型转录调控因子和一种环二-GMP磷酸二酯酶。未甲基化的 Dam 位点偏向于定位在复制末端,这表明它们受到 Dam 甲基化酶的保护。在 Dcm 位点没有检测到胞嘧啶甲基化。
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引用次数: 0
Out of the Silence: Insights into How Genes Escape X-Chromosome Inactivation. 走出沉默洞察基因如何逃避 X 染色体失活。
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-11-23 DOI: 10.3390/epigenomes7040029
Samantha B Peeters, Bronwyn J Posynick, Carolyn J Brown

The silencing of all but one X chromosome in mammalian cells is a remarkable epigenetic process leading to near dosage equivalence in X-linked gene products between the sexes. However, equally remarkable is the ability of a subset of genes to continue to be expressed from the otherwise inactive X chromosome-in some cases constitutively, while other genes are variable between individuals, tissues or cells. In this review we discuss the advantages and disadvantages of the approaches that have been used to identify escapees. The identity of escapees provides important clues to mechanisms underlying escape from XCI, an arena of study now moving from correlation to functional studies. As most escapees show greater expression in females, the not-so-inactive X chromosome is a substantial contributor to sex differences in humans, and we highlight some examples of such impact.

在哺乳动物细胞中,除一条 X 染色体外,所有 X 染色体都处于沉默状态,这是一个显著的表观遗传过程,它导致两性之间 X 连锁基因产物的剂量几乎相等。然而,同样引人注目的是,一部分基因能够继续从原本不活跃的 X 染色体中表达出来--在某些情况下是持续表达,而其他基因则在不同个体、组织或细胞之间变化。在这篇综述中,我们将讨论用于识别转义基因的方法的优缺点。逸出基因的身份为研究从 XCI 中逸出的机制提供了重要线索,这一研究领域目前正从相关性研究转向功能性研究。由于大多数转义因子在女性中的表达量更大,因此并不活跃的 X 染色体是造成人类性别差异的一个重要因素,我们将重点举例说明这种影响。
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引用次数: 0
IndiSPENsable for X Chromosome Inactivation and Gene Silencing 对X染色体失活和基因沉默不可或缺
Q3 GENETICS & HEREDITY Pub Date : 2023-11-02 DOI: 10.3390/epigenomes7040028
Corinne Kaufmann, Anton Wutz
For about 30 years, SPEN has been the subject of research in many different fields due to its variety of functions and its conservation throughout a wide spectrum of species, like worms, arthropods, and vertebrates. To date, 216 orthologues have been documented. SPEN had been studied for its role in gene regulation in the context of cell signaling, including the NOTCH or nuclear hormone receptor signaling pathways. More recently, SPEN has been identified as a major regulator of initiation of chromosome-wide gene silencing during X chromosome inactivation (XCI) in mammals, where its function remains to be fully understood. Dependent on the biological context, SPEN functions via mechanisms which include different domains. While some domains of SPEN are highly conserved in sequence and secondary structure, species-to-species differences exist that might lead to mechanistic differences. Initiation of XCI appears to be different between humans and mice, which raises additional questions about the extent of generalization of SPEN’s function in XCI. In this review, we dissect the mechanism of SPEN in XCI. We discuss its subregions and domains, focusing on its role as a major regulator. We further highlight species-related research, specifically of mouse and human SPEN, with the aim to reveal and clarify potential species-to-species differences in SPEN’s function.
近30年来,由于SPEN的多种功能及其在多种物种(如蠕虫、节肢动物和脊椎动物)中的保护作用,SPEN一直是许多不同领域的研究对象。迄今为止,216个同源词已被记录在案。人们研究了SPEN在细胞信号传导中的基因调控作用,包括NOTCH或核激素受体信号通路。最近,SPEN已被确定为哺乳动物X染色体失活(XCI)期间染色体范围内基因沉默起始的主要调节因子,其功能仍有待充分了解。根据生物学背景,SPEN通过包括不同域的机制起作用。虽然SPEN的一些结构域在序列和二级结构上高度保守,但物种间存在的差异可能导致机制差异。XCI的启动在人类和小鼠之间似乎是不同的,这就提出了关于SPEN在XCI中功能的泛化程度的额外问题。在这篇综述中,我们剖析了SPEN在XCI中的机制。我们将讨论其分区域和领域,重点关注其作为主要监管机构的作用。我们进一步强调物种相关的研究,特别是小鼠和人类的SPEN,旨在揭示和阐明SPEN功能在物种间的潜在差异。
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引用次数: 0
Stress and DNA Methylation of Blood Leukocytes among Pregnant Latina Women 应激与拉丁裔孕妇血液白细胞DNA甲基化
Q3 GENETICS & HEREDITY Pub Date : 2023-11-01 DOI: 10.3390/epigenomes7040027
Veronica Barcelona, Sameera Abuaish, Seonjoo Lee, Sarah Harkins, Ashlie Butler, Benjamin Tycko, Andrea A. Baccarelli, Kate Walsh, Catherine E. Monk
Latinas experience physical and psychological stressors in pregnancy leading to increased morbidity and higher risk for adverse birth outcomes. Epigenetic changes, including DNA methylation (DNAm), have been proposed as markers to create more refined risk stratification, yet few of these studies have examined these changes in Latinas. We conducted a secondary analysis of stored blood leukocytes of Latina women (n = 58) enrolled in a larger National Institutes of Health funded R01 project (2011–2016). We examined DNAm on eight candidate stress genes to compare physically and psychologically stressed participants to healthy (low stress) participants. We found unique CpGs that were differentially methylated in stressed women early- and mid-pregnancy compared to the healthy group, though none remained significant after FDR correction. Both physical and psychological stress were associated with hypomethylation at two consecutive CpG sites on NR3C1 in early pregnancy and one CpG site on NR3C1 in mid-pregnancy before adjustment. Stress was also associated with hypomethylation at two CpG sites on FKBP5 in early and mid-pregnancy but were no longer significant after FDR adjustment. Though we did not find statistically significant differences in DNAm during pregnancy between stressed and healthy women in this sample, signals were consistent with previous findings. Future work in larger samples should further examine the associations between stress and DNAm in pregnancy as this mechanism may explain underlying perinatal health inequities.
拉丁美洲人在怀孕期间经历身体和心理压力,导致发病率增加和不良分娩结局的风险更高。表观遗传变化,包括DNA甲基化(DNAm),已被提出作为创建更精细的风险分层的标记,但这些研究很少检查拉丁美洲人的这些变化。我们对参加美国国立卫生研究院资助的R01项目(2011-2016)的拉丁裔女性(n = 58)的储存血液白细胞进行了二次分析。我们检查了八个候选压力基因的dna,以比较身体和心理上有压力的参与者与健康(低压力)的参与者。我们发现,与健康组相比,压力妇女怀孕早期和中期的独特CpGs甲基化存在差异,但在FDR校正后,没有CpGs甲基化保持显著。生理和心理应激均与妊娠早期NR3C1上两个连续CpG位点的低甲基化和妊娠中期NR3C1上一个CpG位点的低甲基化有关。应激也与妊娠早期和中期FKBP5上两个CpG位点的低甲基化有关,但在FDR调整后不再显著。虽然在这个样本中,我们没有发现压力大的女性和健康女性在怀孕期间的dna有统计学上的显著差异,但信号与之前的发现是一致的。未来在更大样本中的工作应该进一步研究怀孕期间压力和DNAm之间的关系,因为这种机制可能解释潜在的围产期健康不平等。
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引用次数: 0
Correction: Islam, R.A.; Rallis, C. Ribosomal Biogenesis and Heterogeneity in Development, Disease, and Aging. Epigenomes 2023, 7, 17 更正:伊斯兰教,R.A.;核糖体在发育、疾病和衰老中的生物发生和异质性。表观基因组学,2017,7,17
Q3 GENETICS & HEREDITY Pub Date : 2023-10-26 DOI: 10.3390/epigenomes7040026
Rowshan Ara Islam, Charalampos Rallis
23. Akirtava, C.; May, G.E.; McManus, C.J. False-Positive IRESes from Hoxa9 andOther Genes Resulting from Errors in Mam-malian 5’ UTR Annotations [...]
23. Akirtava c;5月,通用电气公司;McManus, c.j。哺乳动物5 ' UTR注释错误导致的Hoxa9和其他基因假阳性IRESes [j]。
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引用次数: 0
Maternal MicroRNA Profile Changes When LH Is Added to the Ovarian Stimulation Protocol: A Pilot Study. 当LH被添加到卵巢刺激方案中时,母体微小RNA图谱的变化:一项初步研究。
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-10-06 DOI: 10.3390/epigenomes7040025
Fani Konstantinidou, Martina Placidi, Giovanna Di Emidio, Liborio Stuppia, Carla Tatone, Valentina Gatta, Paolo Giovanni Artini

While the use of follicle-stimulating hormone (FSH) in ovarian stimulation for in vitro fertilization (IVF) is an established practice, the use of luteinizing hormone (LH) remains debatable. MicroRNAs (miRNAs) are short, endogenous, non-coding transcripts that control a variety of cellular functions, such as gonadotrophin production and follicular development. The goal of this pilot study was to investigate whether the employment of recombinant LH (rLH) in ovarian stimulation protocols results in changes in the miRNA profiles in human oocytes. Patients were divided into two groups: seven received recombinant FSH (rFSH, 225 IU), and six received rFSH (150 IU) plus rLH (75 IU). MiRNA predesigned panels and real-time PCR technology were used to analyze the oocytes retrieved from the follicular ovarian retrieval. Among the miRNAs evaluated, a series of them evidenced upregulation or downregulation in their expression in the FSH plus LH group compared to the FSH group. Considering the results obtained from the functional and network analysis, the different maternal miRNA profiles in the two groups revealed a differential modulation of pathways involved in numerous biological functions. Overall, based on the pathways associated with most of these maternal miRNAs, the presence of LH may result in a different modulation of pathways regulating survival under the control of a Tp53-related mechanism. Interestingly, among the miRNAs differentially expressed in oocytes of the two groups, we have found miRNAs already investigated at ovarian, follicular, oocyte, and embryonic levels: hsa-miR-484, hsa-miR-222, hsa-miR-520d-5p, hsa-miRNA-17, hsa-miR-548, and hsa-miR-140. Thus, investigation into the role of these miRNAs in oocyte molecular pathways may help determine how LH affects oocyte competence and eventually leads to the clinical improvement of IVF.

虽然在体外受精(IVF)的卵巢刺激中使用卵泡刺激素(FSH)是一种既定的做法,但使用促黄体生成素(LH)仍然存在争议。微小RNA(miRNA)是一种短的内源性非编码转录物,控制多种细胞功能,如促性腺激素的产生和卵泡发育。这项初步研究的目的是调查在卵巢刺激方案中使用重组LH(rLH)是否会导致人类卵母细胞中miRNA谱的变化。患者分为两组:7组接受重组FSH(rFSH,225 IU),6组接受rFSH(150 IU)加rLH(75 IU)。MiRNA预先设计的面板和实时PCR技术用于分析从卵泡卵巢取出的卵母细胞。在评估的miRNA中,与FSH组相比,FSH加LH组的一系列miRNA的表达上调或下调。考虑到功能和网络分析的结果,两组中不同的母体miRNA图谱揭示了参与多种生物功能的途径的差异调节。总体而言,基于与大多数这些母体miRNA相关的途径,LH的存在可能导致在Tp53相关机制的控制下对调节存活的途径进行不同的调节。有趣的是,在这两组卵母细胞中差异表达的miRNA中,我们发现已经在卵巢、卵泡、卵母细胞和胚胎水平上研究了miRNA:hsa-miR-484、hsa-miR-222、hsa-miR-520d-5p、hsa-iRNA-17、hsa-micro-548和hsa-miR-140。因此,研究这些miRNA在卵母细胞分子通路中的作用可能有助于确定LH如何影响卵母细胞能力,并最终导致IVF的临床改进。
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引用次数: 0
The ErbB Signaling Network and Its Potential Role in Endometrial Cancer. ErbB信号网络及其在子宫内膜癌症中的潜在作用。
IF 2.5 Q3 GENETICS & HEREDITY Pub Date : 2023-10-01 DOI: 10.3390/epigenomes7040024
Georgios Androutsopoulos, Ioanna Styliara, Evgenia Zarogianni, Nadia Lazurko, George Valasoulis, Georgios Michail, Georgios Adonakis

Endometrial cancer (EC) is the second most common malignancy of the female reproductive system worldwide. The updated EC classification emphasizes the significant role of various signaling pathways such as PIK3CA-PIK3R1-PTEN and RTK/RAS/β-catenin in EC pathogenesis. Some of these pathways are part of the EGF system signaling network, which becomes hyperactivated by various mechanisms and participates in cancer pathogenesis. In EC, the expression of ErbB receptors is significantly different, compared with the premenopausal and postmenopausal endometrium, mainly because of the increased transcriptional activity of ErbB encoding genes in EC cells. Moreover, there are some differences in ErbB-2 receptor profile among EC subgroups that could be explained by the alterations in pathophysiology and clinical behavior of various EC histologic subtypes. The fact that ErbB-2 receptor expression is more common in aggressive EC histologic subtypes (papillary serous and clear cell) could indicate a future role of ErbB-targeted therapies in well-defined EC subgroups with overexpression of ErbB receptors.

癌症(EC)是全球女性生殖系统第二常见的恶性肿瘤。更新的EC分类强调了PIK3CA-PIK3R1-PTEN和RTK/RAS/β-catenin等各种信号通路在EC发病机制中的重要作用。其中一些途径是EGF系统信号网络的一部分,EGF系统的信号网络被各种机制过度激活,并参与癌症的发病机制。在EC中,与绝经前和绝经后子宫内膜相比,ErbB受体的表达显著不同,这主要是因为EC细胞中ErbB编码基因的转录活性增加。此外,EC亚组中ErbB-2受体谱存在一些差异,这可以通过不同EC组织学亚型的病理生理学和临床行为的改变来解释。ErbB-2受体表达在侵袭性EC组织学亚型(乳头状浆液性和透明细胞)中更常见,这一事实可能表明ErbB靶向治疗在ErbB受体过表达的明确EC亚型中的未来作用。
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引用次数: 2
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Epigenomes
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