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神经相关基因启动子的高甲基化与实体瘤中的干性是兼容的。

Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers.

机构信息

Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, P.O. Box 616, 6229 HX, Maastricht, The Netherlands.

Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children's Hospital, 3015 GD, Rotterdam, The Netherlands.

出版信息

Epigenetics Chromatin. 2023 Aug 3;16(1):31. doi: 10.1186/s13072-023-00505-7.

DOI:10.1186/s13072-023-00505-7
PMID:37537688
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10398991/
Abstract

BACKGROUND

DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA).

RESULTS

All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature.

CONCLUSION

Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells.

摘要

背景

DNA 超甲基化是一种调节基因表达的表观遗传特征，其失调在癌症中观察到。此前，我们在结肠癌中鉴定出一种与神经相关的 DNA 超甲基化特征，其中大多数上调和下调的基因在神经系统中具有已知的功能。为了评估这种特征的存在及其与一般癌症发生的相关性，我们考虑了癌症基因组图谱（TCGA）中可用的 16 种实体癌类型。

结果

所有测试的癌症在超甲基化基因中都表现出明显的神经相关基因富集。这种特征已经存在于两种癌前组织类型中，并且不能用潜在的混杂因素（如二价状态或肿瘤纯度）来解释。对结肠癌中与神经相关的 DNA 超甲基化特征的进一步表征表明，该特征特别富集了在神经分化过程中过度表达的基因。最后，对上游调节剂的分析表明，RE1-沉默转录因子（REST）可能是这种 DNA 甲基化特征的介导因子。

结论

我们的研究证实了各种癌症中存在与神经分化相关的基因的与神经相关的 DNA 超甲基化特征指纹，并指出 REST 可能是这种机制的调节因子。我们提出，这种特征指纹表明 DNA 超甲基化参与了癌细胞中神经干细胞的维持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/87c2e309ecc5/13072_2023_505_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/fa3285e7b3ba/13072_2023_505_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/032718fd13eb/13072_2023_505_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/1916d2c6b51d/13072_2023_505_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/c0bc5643940a/13072_2023_505_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/87c2e309ecc5/13072_2023_505_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/fa3285e7b3ba/13072_2023_505_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/032718fd13eb/13072_2023_505_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/1916d2c6b51d/13072_2023_505_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/c0bc5643940a/13072_2023_505_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdcd/10398991/87c2e309ecc5/13072_2023_505_Fig5_HTML.jpg

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1
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2
Nerves in gastrointestinal cancer: from mechanism to modulations.胃肠道癌中的神经：从机制到调控。
Nat Rev Gastroenterol Hepatol. 2022 Dec;19(12):768-784. doi: 10.1038/s41575-022-00669-9. Epub 2022 Sep 2.
3
Neural stemness unifies cell tumorigenicity and pluripotent differentiation potential.神经干/祖细胞特性使细胞致瘤性和多能分化潜能统一。
J Biol Chem. 2022 Jul;298(7):102106. doi: 10.1016/j.jbc.2022.102106. Epub 2022 Jun 4.
4
Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model.神经嵴衍生物的环境线索在胚胎神经母细胞瘤模型中充当转移触发因素。
Nat Commun. 2022 May 10;13(1):2549. doi: 10.1038/s41467-022-30237-3.
5
Suppression of Cell Tumorigenicity by Non-neural Pro-differentiation Factors via Inhibition of Neural Property in Tumorigenic Cells.非神经前分化因子通过抑制致瘤细胞的神经特性来抑制细胞致瘤性。
Front Cell Dev Biol. 2021 Sep 14;9:714383. doi: 10.3389/fcell.2021.714383. eCollection 2021.
6
Neural stemness contributes to cell tumorigenicity.神经干性有助于细胞的致瘤性。
Cell Biosci. 2021 Jan 19;11(1):21. doi: 10.1186/s13578-021-00531-6.
7
Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation.向原始人类多能性的转变反映了泛癌 DNA 高甲基化。
Nat Commun. 2020 Jul 22;11(1):3671. doi: 10.1038/s41467-020-17269-3.
8
MeCP2 and Chromatin Compartmentalization.MeCP2 与染色质区室化。
Cells. 2020 Apr 3;9(4):878. doi: 10.3390/cells9040878.
9
Bivalent promoter hypermethylation in cancer is linked to the H327me3/H3K4me3 ratio in embryonic stem cells.双价启动子超甲基化与胚胎干细胞中的 H327me3/H3K4me3 比值相关。
BMC Biol. 2020 Mar 4;18(1):25. doi: 10.1186/s12915-020-0752-3.
10
Nerves in cancer.癌症中的神经。
Nat Rev Cancer. 2020 Mar;20(3):143-157. doi: 10.1038/s41568-019-0237-2. Epub 2020 Jan 23.