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DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma. 复杂的肿瘤免疫微环境导致的DNA甲基化异质性提示胶质瘤的预后风险。
IF 3.7 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-03-05 DOI: 10.1080/15592294.2024.2318506
Shuangyue Ma, Xu Pan, Jing Gan, Xiaxin Guo, Jiaheng He, Haoyu Hu, Yuncong Wang, Shangwei Ning, Hui Zhi

Gliomas are malignant tumours of the human nervous system with different World Health Organization (WHO) classifications, glioblastoma (GBM) with higher grade and are more malignant than lower-grade glioma (LGG). To dissect how the DNA methylation heterogeneity in gliomas is influenced by the complex cellular composition of the tumour immune microenvironment, we first compared the DNA methylation profiles of purified human immune cells and bulk glioma tissue, stratifying three tumour immune microenvironmental subtypes for GBM and LGG samples from The Cancer Genome Atlas (TCGA). We found that more intermediate methylation sites were enriched in glioma tumour tissues, and used the Proportion of sites with Intermediate Methylation (PIM) to compare intertumoral DNA methylation heterogeneity. A larger PIM score reflected stronger DNA methylation heterogeneity. Enhanced DNA methylation heterogeneity was associated with stronger immune cell infiltration, better survival rates, and slower tumour progression in glioma patients. We then created a Cell-type-associated DNA Methylation Heterogeneity Contribution (CMHC) score to explore the impact of different immune cell types on heterogeneous CpG site (CpGct) in glioma tissues. We identified eight prognosis-related CpGct to construct a risk score: the Cell-type-associated DNA Methylation Heterogeneity Risk (CMHR) score. CMHR was positively correlated with cytotoxic T-lymphocyte infiltration (CTL), and showed better predictive performance for IDH status (AUC = 0.96) and glioma histological phenotype (AUC = 0.81). Furthermore, DNA methylation alterations of eight CpGct might be related to drug treatments of gliomas. In conclusion, we indicated that DNA methylation heterogeneity is associated with a complex tumour immune microenvironment, glioma phenotype, and patient's prognosis.

胶质瘤是人类神经系统的恶性肿瘤,世界卫生组织(WHO)对其进行了不同的分类,胶质母细胞瘤(GBM)的级别较高,比低级胶质瘤(LGG)的恶性程度更高。为了剖析胶质瘤的DNA甲基化异质性如何受到肿瘤免疫微环境复杂细胞组成的影响,我们首先比较了纯化的人类免疫细胞和大块胶质瘤组织的DNA甲基化图谱,并对癌症基因组图谱(TCGA)中的GBM和LGG样本的三种肿瘤免疫微环境亚型进行了分层。我们发现胶质瘤肿瘤组织中富含更多的中间甲基化位点,并使用中间甲基化位点比例(PIM)来比较瘤间DNA甲基化异质性。PIM得分越高,DNA甲基化异质性越强。增强的DNA甲基化异质性与胶质瘤患者更强的免疫细胞浸润、更好的生存率和更慢的肿瘤进展有关。然后,我们创建了细胞类型相关的DNA甲基化异质性贡献(CMHC)评分,以探讨不同免疫细胞类型对胶质瘤组织中异质性CpG位点(CpGct)的影响。我们确定了八个与预后相关的CpGct,构建了一个风险评分:细胞类型相关DNA甲基化异质性风险(CMHR)评分。CMHR与细胞毒性T淋巴细胞浸润(CTL)呈正相关,对IDH状态(AUC = 0.96)和胶质瘤组织学表型(AUC = 0.81)有更好的预测效果。此外,8个CpGct的DNA甲基化改变可能与胶质瘤的药物治疗有关。总之,我们发现DNA甲基化异质性与复杂的肿瘤免疫微环境、胶质瘤表型和患者预后有关。
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引用次数: 0
Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma. N6-甲基腺苷相关 lncRnas 在假性剥脱性青光眼中的作用
IF 3.7 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI: 10.1080/15592294.2024.2348840
Jieying Guan, Xiaohong Chen, Zhidong Li, Shuifeng Deng, Aizezi Wumaier, Yuncheng Ma, Lingling Xie, Shengsong Huang, Yingting Zhu, Yehong Zhuo

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- β signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.

探讨lncRNA m6A甲基化修饰在假性角膜剥脱性青光眼(PXG)患者眼房水(AH)中的作用。选取2021年6月至2021年12月期间接受手术的开角型PXG患者。选择年龄和性别匹配的老年性白内障(ARC)患者作为对照。患者接受了详细的眼科检查。在手术过程中提取 0.05-0.1 ml AH,用于 MeRIP-Seq 和 RNA-Seq。联合分析用于筛选具有不同m6A甲基化修饰和表达的lncRNA。使用在线软件工具绘制lncRNA-miRNA-mRNA网络(ceRNA)。lncRNAs 和 mRNAs 的表达通过实时定量 PCR 进行确认。PXG组共鉴定出4151个lncRNA和4386个相关的m6A甲基化修饰峰。同样,在对照组中检测到了 2490 个 lncRNA 和 2595 个相关的 m6A 甲基化修饰峰。与 ARC 组相比,PXG 组有 234 个高甲基化和 402 个低甲基化的 m6A 峰,其差异有统计学意义(折叠变化(FC)|≥2,p 6A 甲基化和表达同时存在。m6A甲基化修饰可能影响lncRNA的表达,并通过ceRNA网络参与PXG的发病机制。ENST000000485383-hsa miR592-ROCK1 可能是进一步研究 PXG m6A 甲基化的潜在靶途径。
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引用次数: 0
Retracted article: MYCN contributes to the sensitization of acute myelogenous leukemia cells to cisplatin by targeting SRY-box transcription factor 4. 被撤回的文章:MYCN通过靶向SRY-box转录因子4促使急性髓性白血病细胞对顺铂敏感
IF 4.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2021-10-28 DOI: 10.1080/21655979.2021.1997697
Xianbao Huang, Ling Qi, Wei Lu, Ziye Li, Wuping Li, Fei Li

Xianbao Huang, Ling Qi, Wei Lu, Ziye Li, Wuping Li and Fei Li. MYCN contributes to the sensitization of acute myelogenous leukemia cells to cisplatin by targeting SRY-box transcription factor 4. Bioengineered. 2021 Oct. doi: 10.1080/21655979.2021.1997697.Since publication, significant concerns have been raised about the compliance with ethical policies for human research and the integrity of the data reported in the article.When approached for an explanation, the authors provided some original data but were not able to provide all the necessary supporting information. As verifying the validity of published work is core to the scholarly record's integrity, we are retracting the article. All authors listed in this publication have been informed.We have been informed in our decision-making by our editorial policies and the COPE guidelines.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted.'

Xianbao Huang, Ling Qi, Wei Lu, Ziye Li, Wuping Li and Fei Li.MYCN 通过靶向 SRY-box 转录因子 4 使急性髓性白血病细胞对顺铂敏感。生物工程。2021年10月。doi: 10.1080/21655979.2021.1997697.自发表以来,人们对该文是否符合人类研究伦理政策以及文中报告数据的完整性表示了极大的关注。当要求作者做出解释时,作者提供了一些原始数据,但未能提供所有必要的支持信息。由于核实发表作品的有效性是学术记录完整性的核心,我们将撤回这篇文章。我们的决策参考了我们的编辑政策和 COPE 指南。被撤稿的文章将继续在线,以保持学术记录,但每页上都会有数字水印'Retracted'(撤稿)。
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引用次数: 0
Statement of Retraction: Knockdown of long non-coding RNA AGAP2-AS1 suppresses the proliferation and metastasis of glioma by targeting microRNA-497-5p. 撤回声明:敲除长非编码RNA AGAP2-AS1通过靶向microRNA-497-5p抑制胶质瘤的增殖和转移
IF 4.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-01-18 DOI: 10.1080/21655979.2024.2302648
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引用次数: 0
Statement of Retraction: MYCN contributes to the sensitization of acute myelogenous leukemia cells to cisplatin by targeting SRY-box transcription factor 4. 撤回声明:MYCN 通过靶向 SRY-box 转录因子 4 使急性髓性白血病细胞对顺铂敏感。
IF 4.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-02-01 DOI: 10.1080/21655979.2024.2302650
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引用次数: 0
Calling the question: what is mammalian transgenerational epigenetic inheritance? 提出问题:什么是哺乳动物的跨代表观遗传?
IF 3.7 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI: 10.1080/15592294.2024.2333586
Hasan Khatib, Jessica Townsend, Melissa A Konkel, Gabi Conidi, Julia A Hasselkus

While transgenerational epigenetic inheritance has been extensively documented in plants, nematodes, and fruit flies, its existence in mammals remains controversial. Several factors have contributed to this debate, including the lack of a clear distinction between intergenerational and transgenerational epigenetic inheritance (TEI), the inconsistency of some studies, the potential confounding effects of in-utero vs. epigenetic factors, and, most importantly, the biological challenge of epigenetic reprogramming. Two waves of epigenetic reprogramming occur: in the primordial germ cells and the developing embryo after fertilization, characterized by global erasure of DNA methylation and remodelling of histone modifications. Consequently, TEI can only occur if specific genetic regions evade this reprogramming and persist through embryonic development. These challenges have revived the long-standing debate about the possibility of inheriting acquired traits, which has been strongly contested since the Lamarckian and Darwinian eras. As a result, coupled with the absence of universally accepted criteria for transgenerational epigenetic studies, a vast body of literature has emerged claiming evidence of TEI. Therefore, the goal of this study is to advocate for establishing fundamental criteria that must be met for a study to qualify as evidence of TEI. We identified five criteria based on the consensus of studies that critically evaluated TEI. To assess whether published original research papers adhere to these criteria, we examined 80 studies that either claimed or were cited as supporting TEI. The findings of this analysis underscore the widespread confusion in this field and highlight the urgent need for a unified scientific consensus on TEI requirements.

虽然转代表观遗传在植物、线虫和果蝇中得到了广泛的记录,但其在哺乳动物中的存在仍然存在争议。导致这一争论的因素有很多,包括缺乏对代际遗传和跨代表观遗传(TEI)的明确区分、一些研究的不一致性、胎内因素与表观遗传因素的潜在混杂效应,以及最重要的表观遗传重编程的生物学挑战。表观遗传重编程有两波:原始生殖细胞和受精后发育的胚胎,其特点是 DNA 甲基化的全面清除和组蛋白修饰的重塑。因此,只有当特定基因区域逃避这种重编程并在胚胎发育过程中持续存在时,才能发生 TEI。这些挑战再次引发了关于后天性状遗传可能性的长期争论,这一争论自拉马克和达尔文时代以来就一直存在。因此,加上跨代表观遗传研究缺乏公认的标准,出现了大量声称有 TEI 证据的文献。因此,本研究的目标是倡导建立基本标准,一项研究必须符合这些标准才有资格成为 TEI 的证据。我们根据批判性评估 TEI 的研究共识,确定了五项标准。为了评估已发表的原创研究论文是否符合这些标准,我们研究了 80 项声称或被引用为支持 TEI 的研究。这项分析的结果凸显了该领域普遍存在的混乱现象,并强调了就 TEI 要求达成统一科学共识的迫切需要。
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引用次数: 0
Non-coding 886 (nc886/vtRNA2-1), the epigenetic odd duck - implications for future studies. 非编码 886(nc886/vtRNA2-1),表观遗传学的怪鸭--对未来研究的启示。
IF 3.7 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI: 10.1080/15592294.2024.2332819
Emma Raitoharju, Sonja Rajić, Saara Marttila

Non-coding 886 (nc886, vtRNA2-1) is the only human polymorphically imprinted gene, in which the methylation status is not determined by genetics. Existing literature regarding the establishment, stability and consequences of the methylation pattern, as well as the nature and function of the nc886 RNAs transcribed from the locus, are contradictory. For example, the methylation status of the locus has been reported to be stable through life and across somatic tissues, but also susceptible to environmental effects. The nature of the produced nc886 RNA(s) has been redefined multiple times, and in carcinogenesis, these RNAs have been reported to have conflicting roles. In addition, due to the bimodal methylation pattern of the nc886 locus, traditional genome-wide methylation analyses can lead to false-positive results, especially in smaller datasets. Herein, we aim to summarize the existing literature regarding nc886, discuss how the characteristics of nc886 give rise to contradictory results, as well as to reinterpret, reanalyse and, where possible, replicate the results presented in the current literature. We also introduce novel findings on how the distribution of the nc886 methylation pattern is associated with the geographical origins of the population and describe the methylation changes in a large variety of human tumours. Through the example of this one peculiar genetic locus and RNA, we aim to highlight issues in the analysis of DNA methylation and non-coding RNAs in general and offer our suggestions for what should be taken into consideration in future analyses.

非编码 886(nc886,vtRNA2-1)是人类唯一的多态印记基因,其甲基化状态不是由遗传决定的。有关甲基化模式的建立、稳定性和后果,以及从该基因座转录的 nc886 RNA 的性质和功能的现有文献相互矛盾。例如,据报道,该基因座的甲基化状态在整个生命过程和不同的体细胞组织中都是稳定的,但也容易受到环境的影响。产生的 nc886 RNA 的性质已被多次重新定义,据报道,这些 RNA 在致癌过程中的作用相互矛盾。此外,由于 nc886 位点的双峰甲基化模式,传统的全基因组甲基化分析可能会导致假阳性结果,尤其是在较小的数据集中。在此,我们旨在总结有关 nc886 的现有文献,讨论 nc886 的特征如何导致相互矛盾的结果,并重新解释、分析和尽可能复制现有文献中的结果。我们还介绍了关于 nc886 甲基化模式的分布如何与人口的地理来源相关联的新发现,并描述了多种人类肿瘤中的甲基化变化。通过这个特殊基因位点和 RNA 的例子,我们旨在强调 DNA 甲基化和非编码 RNA 分析中的一般问题,并就未来分析中应考虑的因素提出我们的建议。
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引用次数: 0
Statement of Retraction: Dehydroevodiamine suppresses inflammatory responses in adjuvant-induced arthritis rats and human fibroblast-like synoviocytes. 撤回声明:脱氢乙二胺可抑制佐剂诱导的关节炎大鼠和人类成纤维细胞样滑膜细胞的炎症反应。
IF 4.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-02-20 DOI: 10.1080/21655979.2024.2299578
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引用次数: 0
Statement of Retraction: Forkhead-box C1 attenuates high glucose-induced trophoblast cell injury during gestational diabetes mellitus via activating adenosine monophosphate-activated protein kinase through regulating fibroblast growth factor 19. 撤回声明:叉头盒C1通过调节成纤维细胞生长因子19激活单磷酸腺苷激活的蛋白激酶,从而减轻妊娠糖尿病期间高糖诱导的滋养层细胞损伤。
IF 4.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-02-20 DOI: 10.1080/21655979.2024.2299608
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引用次数: 0
Statement of Retraction: Knockdown of small nucleolar RNA host gene 10 (SNHG10) alleviates the injury of human neuroblastoma cells via the miR-1277-5p/insulin substrate receptor 2 axis. 撤回声明:敲除小核仁RNA宿主基因10(SNHG10)可通过miR-1277-5p/胰岛素底物受体2轴减轻人神经母细胞瘤细胞的损伤。
IF 4.9 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-12-01 Epub Date: 2024-02-20 DOI: 10.1080/21655979.2024.2299623
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引用次数: 0
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