• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人类乳腺癌的综合表观遗传学：靶向基因、microRNAs 和蛋白质在去甲基化处理后的综合研究。

Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.

机构信息

Laboratory for Gynecological Oncology, Department of Biomedicine/Women's Hospital, University of Basel, Basel, Switzerland.

出版信息

PLoS One. 2011;6(11):e27355. doi: 10.1371/journal.pone.0027355. Epub 2011 Nov 4.

DOI:10.1371/journal.pone.0027355
PMID:22076154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3208622/
Abstract

BACKGROUND

The contribution of aberrant DNA methylation in silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations are reversible, it became of interest to determine the effects of the 5-aza-2'-deoxycytidine (DAC) demethylation therapy in breast cancer at different molecular levels.

METHODS AND FINDINGS

Here we investigate a synoptic model to predict complete DAC treatment effects at the level of genes, microRNAs and proteins for several human breast cancer lines. The present study assessed an effective treatment dosage based on the cell viability, cytotoxicity, apoptosis and methylation assays for the investigated cell lines. A highly aggressive and a non-aggressive cell line were investigated using omics approaches such as MALDI-TOF MS, mRNA- and microRNA expression arrays, 2-D gel electrophoresis and LC-MS-MS. Complete molecular profiles including the biological interaction and possible early and late systematic stable or transient effects of the methylation inhibition were determined. Beside the activation of several epigenetically suppressed TSGs, we also showed significant dysregulation of some important oncogenes, oncomiRs and oncosuppressors miRNAs as well as drug tolerance genes/miRNAs/proteins.

CONCLUSIONS

In the present study, the results denote some new molecular DAC targets and pathways based on the chemical modification of DNA methylation in breast cancer. The outlined approach might prove to be useful as an epigenetic treatment model also for other human solid tumors in the management of cancer patients.

摘要

背景

已经研究了异常 DNA 甲基化对肿瘤抑制基因 (TSG) 和 microRNAs 沉默的贡献。由于这些表观遗传改变是可逆的，因此人们有兴趣在不同的分子水平上确定 5-氮杂-2'-脱氧胞苷 (DAC) 去甲基化治疗对乳腺癌的影响。

方法和发现

在这里，我们研究了一个综合模型，以预测几种人乳腺癌系在基因、microRNAs 和蛋白质水平上的完全 DAC 治疗效果。本研究根据细胞活力、细胞毒性、细胞凋亡和甲基化测定评估了针对研究细胞系的有效治疗剂量。使用 MALDI-TOF MS、mRNA 和 microRNA 表达阵列、2-D 凝胶电泳和 LC-MS-MS 等组学方法研究了一个高度侵袭性和非侵袭性的细胞系。确定了完整的分子谱，包括生物相互作用以及甲基化抑制的可能早期和晚期系统稳定或瞬时效应。除了激活几个被表观遗传抑制的 TSG 外，我们还发现了一些重要的癌基因、oncomiRs 和 oncosuppressors miRNAs 以及药物耐受基因/miRNAs/蛋白质的显著失调。

结论

在本研究中，结果表明基于乳腺癌中 DNA 甲基化的化学修饰，存在一些新的分子 DAC 靶标和途径。所概述的方法可能被证明对癌症患者的人类实体瘤的其他表观遗传治疗模型也有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/c7e2ea3f1b1d/pone.0027355.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/c909c3a9406b/pone.0027355.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/dbd69193b4d8/pone.0027355.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/df77485a5e25/pone.0027355.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/1601dd54e30e/pone.0027355.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/078f34d072cc/pone.0027355.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/ea8f4a1fb8fa/pone.0027355.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/dfcc53690a76/pone.0027355.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/c7e2ea3f1b1d/pone.0027355.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/c909c3a9406b/pone.0027355.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/dbd69193b4d8/pone.0027355.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/df77485a5e25/pone.0027355.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/1601dd54e30e/pone.0027355.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/078f34d072cc/pone.0027355.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/ea8f4a1fb8fa/pone.0027355.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/dfcc53690a76/pone.0027355.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6299/3208622/c7e2ea3f1b1d/pone.0027355.g008.jpg

相似文献

1
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.人类乳腺癌的综合表观遗传学：靶向基因、microRNAs 和蛋白质在去甲基化处理后的综合研究。
PLoS One. 2011;6(11):e27355. doi: 10.1371/journal.pone.0027355. Epub 2011 Nov 4.
2
Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer.基因组筛选发现受去甲基化作用上调的基因，揭示了乳腺癌中表观遗传沉默的新靶点。
Breast Cancer Res Treat. 2010 Aug;122(3):699-710. doi: 10.1007/s10549-009-0600-1. Epub 2009 Oct 27.
3
Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists.5-氮杂-2'-脱氧胞苷在结直肠癌细胞中的去甲基化作用靶向基因组 DNA，而启动子 CpG 岛的甲基化持续存在。
BMC Cancer. 2010 Jul 12;10:366. doi: 10.1186/1471-2407-10-366.
4
Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis.PRKD1启动子表观遗传沉默的药理学逆转可阻断乳腺肿瘤细胞的侵袭和转移。
Breast Cancer Res. 2013 Aug 23;15(2):R66. doi: 10.1186/bcr3460.
5
Growth inhibition of human cancer cells by 5-aza-2'-deoxycytidine does not correlate with its effects on INK4a/ARF expression or initial promoter methylation status.5-氮杂-2'-脱氧胞苷对人癌细胞的生长抑制作用与其对INK4a/ARF表达或初始启动子甲基化状态的影响无关。
Mol Cancer Ther. 2009 Apr;8(4):779-85. doi: 10.1158/1535-7163.MCT-08-0926.
6
Epigenetics and miRNA as predictive markers and targets for lung cancer chemotherapy.表观遗传学和微小RNA作为肺癌化疗的预测标志物及靶点
Cancer Biol Ther. 2015;16(7):1056-70. doi: 10.1080/15384047.2015.1046023.
7
MicroRNA 345, a methylation-sensitive microRNA is involved in cell proliferation and invasion in human colorectal cancer.微小 RNA345 是一种甲基化敏感的微小 RNA，参与人结直肠癌细胞的增殖和侵袭。
Carcinogenesis. 2011 Aug;32(8):1207-15. doi: 10.1093/carcin/bgr114. Epub 2011 Jun 10.
8
5-aza-2'-Deoxycytidine enhances the radiosensitivity of breast cancer cells.5-氮杂-2'-脱氧胞苷增强乳腺癌细胞的放射敏感性。
Cancer Biother Radiopharm. 2013 Feb;28(1):34-44. doi: 10.1089/cbr.2012.1170. Epub 2012 Aug 23.
9
Genome-wide methylation profiling of ovarian cancer patient-derived xenografts treated with the demethylating agent decitabine identifies novel epigenetically regulated genes and pathways.用去甲基化剂地西他滨处理的卵巢癌患者来源异种移植瘤的全基因组甲基化分析鉴定了新的表观遗传调控基因和通路。
Genome Med. 2016 Oct 20;8(1):107. doi: 10.1186/s13073-016-0361-5.
10
Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer.在人类乳腺癌中，受体酪氨酸激酶EphA5常因启动子甲基化而发生表观遗传失活。
Hum Pathol. 2010 Jan;41(1):48-58. doi: 10.1016/j.humpath.2009.06.007. Epub 2009 Sep 5.

引用本文的文献

1
Ketone body, as an emerging modulator of metabolic reprogramming and epigenetics in breast cancer.酮体作为乳腺癌中代谢重编程和表观遗传学的一种新兴调节因子。
Iran J Basic Med Sci. 2025;28(9):1129-1139. doi: 10.22038/ijbms.2025.84064.18185.
2
Applications of CRISPR-Cas9 in mitigating cellular senescence and age-related disease progression.CRISPR-Cas9在减轻细胞衰老和与年龄相关疾病进展方面的应用。
Clin Exp Med. 2025 Jul 8;25(1):237. doi: 10.1007/s10238-025-01771-3.
3
Epigenetic regulation of breast cancer metastasis.乳腺癌转移的表观遗传调控。

本文引用的文献

1
Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer.抑癌基因在关键调控通路中的异常甲基化与乳腺癌液体活检的开发
PLoS One. 2011 Jan 24;6(1):e16080. doi: 10.1371/journal.pone.0016080.
2
Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease.Cx43 抑制了人类疾病 Cx43 突变小鼠模型中的乳腺肿瘤向肺部转移。
Oncogene. 2011 Apr 7;30(14):1681-92. doi: 10.1038/onc.2010.551. Epub 2010 Dec 13.
3
Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.
Cancer Metastasis Rev. 2024 Jun;43(2):597-619. doi: 10.1007/s10555-023-10146-7. Epub 2023 Oct 19.
4
Epigenetics and environment in breast cancer: New paradigms for anti-cancer therapies.乳腺癌中的表观遗传学与环境：抗癌治疗的新范式
Front Oncol. 2022 Sep 15;12:971288. doi: 10.3389/fonc.2022.971288. eCollection 2022.
5
CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis.CELF 家族蛋白在癌症中的作用：聚焦于 RNA 结合蛋白/非编码 RNA 调控轴。
Int J Mol Sci. 2021 Oct 14;22(20):11056. doi: 10.3390/ijms222011056.
6
Epigenetic Regulation in Breast Cancer.乳腺癌中的表观遗传调控。
Adv Exp Med Biol. 2021;1187:103-119. doi: 10.1007/978-981-32-9620-6_5.
7
Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer.乳腺癌中甲基化驱动基因的全基因组分析及用于预后预测的八基因panel的鉴定
Front Genet. 2020 Apr 21;11:301. doi: 10.3389/fgene.2020.00301. eCollection 2020.
8
Single-cell analysis of tumors: Creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells.肿瘤的单细胞分析：为癌症干细胞和肿瘤浸润免疫细胞的分子生物标志物发现创造新价值。
World J Stem Cells. 2018 Nov 26;10(11):160-171. doi: 10.4252/wjsc.v10.i11.160.
9
Prediction of Potential Small Molecule-Associated MicroRNAs Using Graphlet Interaction.使用图let相互作用预测潜在的小分子相关微小RNA
Front Pharmacol. 2018 Oct 15;9:1152. doi: 10.3389/fphar.2018.01152. eCollection 2018.
10
Loss of mdig expression enhances DNA and histone methylation and metastasis of aggressive breast cancer.MDIG 表达缺失增强侵袭性乳腺癌的 DNA 和组蛋白甲基化及转移。
Signal Transduct Target Ther. 2018 Sep 21;3:25. doi: 10.1038/s41392-018-0027-4. eCollection 2018.
小分子和环肽拮抗剂与 CXCR4 趋化因子 GPCR 的结构。
Science. 2010 Nov 19;330(6007):1066-71. doi: 10.1126/science.1194396. Epub 2010 Oct 7.
4
The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models.《基因芯片质量控制（MAQC）-II 研究：基于基因芯片的预测模型的开发和验证的常见实践》。
Nat Biotechnol. 2010 Aug;28(8):827-38. doi: 10.1038/nbt.1665. Epub 2010 Jul 30.
5
miR-183 inhibits TGF-beta1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells.miR-183 通过下调 PDCD4 表达抑制 TGF-β1 诱导的人肝癌细胞凋亡。
BMC Cancer. 2010 Jul 6;10:354. doi: 10.1186/1471-2407-10-354.
6
CXCL12 (SDF-1)/CXCR4 pathway in cancer.CXCL12（SDF-1）/CXCR4 通路与癌症。
Clin Cancer Res. 2010 Jun 1;16(11):2927-31. doi: 10.1158/1078-0432.CCR-09-2329. Epub 2010 May 18.
7
MicroRNA and drug resistance.miRNA 与药物耐药性。
Cancer Gene Ther. 2010 Aug;17(8):523-31. doi: 10.1038/cgt.2010.18. Epub 2010 May 14.
8
Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations.乳腺癌患者中 TP53 调控通路甲基化谱和 mtDNA 改变与 TP53 基因突变缺失的关系。
Hum Mol Genet. 2010 Aug 1;19(15):2936-46. doi: 10.1093/hmg/ddq199. Epub 2010 May 12.
9
The therapeutic promise of the cancer stem cell concept.癌症干细胞概念的治疗前景。
J Clin Invest. 2010 Jan;120(1):41-50. doi: 10.1172/JCI41004.
10
Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression.Satb1和Satb2调节胚胎干细胞分化及Nanog表达。
Genes Dev. 2009 Nov 15;23(22):2625-38. doi: 10.1101/gad.1815709.