• 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

昼夜节律基因Arntl2是雌激素受体阴性乳腺癌的转移易感基因。

The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer.

作者信息

Ha Ngoc-Han, Long Jirong, Cai Qiuyin, Shu Xiao Ou, Hunter Kent W

机构信息

Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

出版信息

PLoS Genet. 2016 Sep 22;12(9):e1006267. doi: 10.1371/journal.pgen.1006267. eCollection 2016 Sep.

DOI:10.1371/journal.pgen.1006267
PMID:27656887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5033489/
Abstract

Breast cancer mortality is primarily due to metastasis rather than primary tumors, yet relatively little is understood regarding the etiology of metastatic breast cancer. Previously, using a mouse genetics approach, we demonstrated that inherited germline polymorphisms contribute to metastatic disease, and that these single nucleotide polymorphisms (SNPs) could be used to predict outcome in breast cancer patients. In this study, a backcross between a highly metastatic (FVB/NJ) and low metastatic (MOLF/EiJ) mouse strain identified Arntl2, a gene encoding a circadian rhythm transcription factor, as a metastasis susceptibility gene associated with progression, specifically in estrogen receptor-negative breast cancer patients. Integrated whole genome sequence analysis with DNase hypersensitivity sites reveals SNPs in the predicted promoter of Arntl2. Using CRISPR/Cas9-mediated substitution of the MOLF promoter, we demonstrate that the SNPs regulate Arntl2 transcription and affect metastatic burden. Finally, analysis of SNPs associated with ARNTL2 expression in human breast cancer patients revealed reproducible associations of ARNTL2 expression quantitative trait loci (eQTL) SNPs with disease-free survival, consistent with the mouse studies.

摘要

乳腺癌死亡率主要归因于转移而非原发性肿瘤，然而对于转移性乳腺癌的病因了解相对较少。此前，我们采用小鼠遗传学方法证明，遗传种系多态性会导致转移性疾病，并且这些单核苷酸多态性（SNP）可用于预测乳腺癌患者的预后。在本研究中，一种高转移性（FVB/NJ）和低转移性（MOLF/EiJ）小鼠品系之间的回交鉴定出Arntl2，这是一个编码昼夜节律转录因子的基因，是与进展相关的转移易感基因，特别是在雌激素受体阴性的乳腺癌患者中。将全基因组序列分析与DNase超敏位点整合，揭示了Arntl2预测启动子中的SNP。使用CRISPR/Cas9介导的MOLF启动子替换，我们证明这些SNP调节Arntl2转录并影响转移负担。最后，对人类乳腺癌患者中与ARNTL2表达相关的SNP进行分析，发现ARNTL2表达数量性状位点（eQTL）SNP与无病生存期存在可重复的关联，这与小鼠研究结果一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/b5fff9e7f3e0/pgen.1006267.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/421a1367c16e/pgen.1006267.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/79a7a627725c/pgen.1006267.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/c492f5884c2c/pgen.1006267.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/5604874edec1/pgen.1006267.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/b5fff9e7f3e0/pgen.1006267.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/421a1367c16e/pgen.1006267.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/79a7a627725c/pgen.1006267.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/c492f5884c2c/pgen.1006267.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/5604874edec1/pgen.1006267.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/528e/5033489/b5fff9e7f3e0/pgen.1006267.g005.jpg

相似文献

1
The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer.昼夜节律基因Arntl2是雌激素受体阴性乳腺癌的转移易感基因。
PLoS Genet. 2016 Sep 22;12(9):e1006267. doi: 10.1371/journal.pgen.1006267. eCollection 2016 Sep.
2
ARNTL2 is a Prognostic Biomarker and Correlates with Immune Cell Infiltration in Triple-Negative Breast Cancer.ARNTL2是三阴性乳腺癌的一种预后生物标志物，且与免疫细胞浸润相关。
Pharmgenomics Pers Med. 2021 Nov 10;14:1425-1440. doi: 10.2147/PGPM.S331431. eCollection 2021.
3
Loss of circadian clock gene expression is associated with tumor progression in breast cancer.昼夜节律时钟基因表达的丧失与乳腺癌的肿瘤进展相关。
Cell Cycle. 2014;13(20):3282-91. doi: 10.4161/15384101.2014.954454.
4
The circadian rhythm key gene : a novel prognostic biomarker for immunosuppressive tumor microenvironment identification and immunotherapy outcome prediction in human cancers.昼夜节律关键基因：一种新型的预后生物标志物，用于鉴定人类癌症中的免疫抑制性肿瘤微环境和预测免疫治疗效果。
Front Immunol. 2023 May 19;14:1115809. doi: 10.3389/fimmu.2023.1115809. eCollection 2023.
5
Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies.昼夜节律途径遗传变异与癌症风险：来自全基因组关联研究的证据。
BMC Med. 2018 Feb 19;16(1):20. doi: 10.1186/s12916-018-1010-1.
6
ARNTL2 upregulation of ACOT7 promotes NSCLC cell proliferation through inhibition of apoptosis and ferroptosis.ARNTL2 上调 ACOT7 通过抑制细胞凋亡和铁死亡促进非小细胞肺癌细胞增殖。
BMC Mol Cell Biol. 2023 Mar 31;24(1):14. doi: 10.1186/s12860-022-00450-5.
7
Relation between single nucleotide polymorphisms in circadian clock relevant genes and cholesterol metabolism.生物钟相关基因单核苷酸多态性与胆固醇代谢的关系。
Mol Genet Metab. 2023 Apr;138(4):107561. doi: 10.1016/j.ymgme.2023.107561. Epub 2023 Mar 27.
8
Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer.跨种族预测表达全基因组关联分析确定了雌激素受体阴性乳腺癌的一个基因。
PLoS Genet. 2017 Sep 28;13(9):e1006727. doi: 10.1371/journal.pgen.1006727. eCollection 2017 Sep.
9
The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis.昼夜节律转录因子ARNTL2受人体白色脂肪组织中减肥干预措施的调节，并抑制脂肪生成。
Cell Death Discov. 2022 Nov 3;8(1):443. doi: 10.1038/s41420-022-01239-3.
10
Identification of the transcription factor ARNTL2 as a candidate gene for the type 1 diabetes locus Idd6.转录因子ARNTL2被鉴定为1型糖尿病位点Idd6的候选基因。
Hum Mol Genet. 2006 Sep 15;15(18):2732-42. doi: 10.1093/hmg/ddl209. Epub 2006 Aug 7.

引用本文的文献

1
Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications.癌症中的神经-免疫相互作用：机制与治疗意义
Signal Transduct Target Ther. 2025 Jun 2;10(1):176. doi: 10.1038/s41392-025-02241-8.
2
Integrative analysis of a novel signature incorporating metabolism and stemness-related genes for risk stratification and assessing clinical outcomes and therapeutic responses in lung adenocarcinoma.整合分析一种包含代谢和干性相关基因的新型特征用于肺腺癌的风险分层、评估临床结局和治疗反应
BMC Cancer. 2025 Apr 1;25(1):591. doi: 10.1186/s12885-025-13984-6.
3
ARNTL2: a key player in promoting tumor aggressiveness in papillary thyroid cancer.

本文引用的文献

1
An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency.由Arntl2驱动的分泌组促成肺腺癌转移自给自足。
Cancer Cell. 2016 May 9;29(5):697-710. doi: 10.1016/j.ccell.2016.03.003. Epub 2016 Apr 14.
2
An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes.乳腺癌转移易感性基因的全基因组综合系统遗传学筛查
PLoS Genet. 2016 Apr 13;12(4):e1005989. doi: 10.1371/journal.pgen.1005989. eCollection 2016 Apr.
3
PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription.
芳香烃受体核转运蛋白样蛋白2（ARNTL2）：促进甲状腺乳头状癌肿瘤侵袭性的关键因子
Transl Cancer Res. 2025 Jan 31;14(1):522-534. doi: 10.21037/tcr-24-1205. Epub 2025 Jan 23.
4
Resf1 is a compound G4 quadruplex-associated tumor suppressor for triple negative breast cancer.Resf1 是一种与 G4 四链体相关的抑癌化合物，可用于三阴性乳腺癌。
PLoS Genet. 2024 May 9;20(5):e1011236. doi: 10.1371/journal.pgen.1011236. eCollection 2024 May.
5
Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib.ARNTL2 通过激活 PI3K/AKT 信号通路增强细胞糖酵解作用，并增强胰腺腺癌细胞对厄洛替尼的敏感性。
Mol Cancer. 2024 Mar 8;23(1):48. doi: 10.1186/s12943-024-01965-5.
6
ARNTL2 upregulation of ACOT7 promotes NSCLC cell proliferation through inhibition of apoptosis and ferroptosis.ARNTL2 上调 ACOT7 通过抑制细胞凋亡和铁死亡促进非小细胞肺癌细胞增殖。
BMC Mol Cell Biol. 2023 Mar 31;24(1):14. doi: 10.1186/s12860-022-00450-5.
7
Prognostic assessment capability of a five-gene signature in pancreatic cancer: a machine learning based-study.基于机器学习的五基因标志物对胰腺癌预后评估能力的研究。
BMC Gastroenterol. 2023 Mar 11;23(1):68. doi: 10.1186/s12876-023-02700-y.
8
Major roles of the circadian clock in cancer.昼夜节律钟在癌症中的主要作用。
Cancer Biol Med. 2023 Jan 12;20(1):1-24. doi: 10.20892/j.issn.2095-3941.2022.0474.
9
Development and Validation of a Novel Circadian Rhythm-Related Signature to Predict the Prognosis of the Patients with Hepatocellular Carcinoma.开发和验证一种新型与昼夜节律相关的特征签名，以预测肝细胞癌患者的预后。
Biomed Res Int. 2022 Aug 12;2022:4263261. doi: 10.1155/2022/4263261. eCollection 2022.
10
Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.肿瘤微环境中宿主 CLIC4 的表达对于乳腺癌的转移能力至关重要。
PLoS Genet. 2022 Jun 21;18(6):e1010271. doi: 10.1371/journal.pgen.1010271. eCollection 2022 Jun.
PARP1 和 CTCF 介导的核纤层活跃和抑制染色质之间的相互作用促进振荡转录。
Mol Cell. 2015 Sep 17;59(6):984-97. doi: 10.1016/j.molcel.2015.07.019. Epub 2015 Aug 27.
4
Loss of circadian clock gene expression is associated with tumor progression in breast cancer.昼夜节律时钟基因表达的丧失与乳腺癌的肿瘤进展相关。
Cell Cycle. 2014;13(20):3282-91. doi: 10.4161/15384101.2014.954454.
5
Circadian disrupting exposures and breast cancer risk: a meta-analysis.昼夜节律紊乱暴露与乳腺癌风险：一项荟萃分析。
Int Arch Occup Environ Health. 2015 Jul;88(5):533-47. doi: 10.1007/s00420-014-0986-x. Epub 2014 Sep 27.
6
An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease.一个综合系统遗传学筛选揭示了遗传易感性转移性疾病的转录结构。
Genome Res. 2014 Feb;24(2):227-40. doi: 10.1101/gr.166223.113. Epub 2013 Dec 9.
7
BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.BRD4短异构体在核膜内表面与RRP1B、SIPA1以及LINC复合物的组分相互作用。
PLoS One. 2013 Nov 19;8(11):e80746. doi: 10.1371/journal.pone.0080746. eCollection 2013.
8
Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts.乳腺癌基因工程小鼠模型的转录组分类可识别出对应的人类亚型。
Genome Biol. 2013 Nov 12;14(11):R125. doi: 10.1186/gb-2013-14-11-r125.
9
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.遗传背景可能有助于 PAM50 基因表达乳腺癌亚型的分类。
PLoS One. 2013 Aug 28;8(8):e72287. doi: 10.1371/journal.pone.0072287. eCollection 2013.
10
Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts.挪威夜班护士昼夜节律相关基因多态性与乳腺癌风险分析。
Breast Cancer Res. 2013;15(4):R53. doi: 10.1186/bcr3445.