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SOX17甲基化抑制其在肺癌中对Wnt信号通路的拮抗作用。

SOX17 methylation inhibits its antagonism of Wnt signaling pathway in lung cancer.

作者信息

Yin Dongtao, Jia Yan, Yu Yuanzi, Brock Malcolm V, Herman James G, Han Chao, Su Xiaomo, Liu Yang, Guo Mingzhou

机构信息

Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Discov Med. 2012 Jul;14(74):33-40.

PMID:22846201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4061568/
Abstract

The purpose of this study was to explore epigenetic changes and functions of SOX17 in human lung cancer. Five lung cancer cell lines and 88 primary lung cancer samples were examined in this study. Methylation-specific polymerase chain reaction (MSP), semi-quantitative reverse-transcription PCR, immunohistochemistry, luciferase reporter assays, colony-formation assays, and western blotting were used to analyze methylation changes and functions of SOX17 in lung cancer. SOX17 methylation was found in 60.2% of primary human lung cancer samples, and promoter region methylation of SOX17 silenced its expression. SOX17 methylation was associated with female patients and lung cancer differentiation. Colony-formation assays revealed that SOX17 suppressed lung cancer cell proliferation. Re-expression of SOX17 inhibited Wnt signaling in H23 lung cancer cell line. SOX17 acts as a Wnt signaling inhibitor.

摘要

本研究的目的是探讨SOX17在人类肺癌中的表观遗传变化及其功能。本研究检测了五种肺癌细胞系和88例原发性肺癌样本。采用甲基化特异性聚合酶链反应(MSP)、半定量逆转录PCR、免疫组织化学、荧光素酶报告基因检测、集落形成检测和蛋白质免疫印迹法分析SOX17在肺癌中的甲基化变化及其功能。在60.2%的原发性人类肺癌样本中发现了SOX17甲基化,且SOX17的启动子区域甲基化使其表达沉默。SOX17甲基化与女性患者及肺癌分化相关。集落形成检测显示,SOX17抑制肺癌细胞增殖。SOX17的重新表达抑制了H23肺癌细胞系中的Wnt信号传导。SOX17作为一种Wnt信号抑制剂发挥作用。

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本文引用的文献

1
Epigenetic regulation of DACT2, a key component of the Wnt signalling pathway in human lung cancer.人类肺癌中 Wnt 信号通路关键组分 DACT2 的表观遗传调控。
J Pathol. 2013 Jun;230(2):194-204. doi: 10.1002/path.4073.
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Epigenetic control of gene expression in the lung.肺中基因表达的表观遗传控制。
Am J Respir Crit Care Med. 2011 May 15;183(10):1295-301. doi: 10.1164/rccm.201010-1579PP.
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SOX17 antagonizes WNT/β-catenin signaling pathway in hepatocellular carcinoma.SOX17 在肝癌中拮抗 WNT/β-catenin 信号通路。
Epigenetics. 2010 Nov-Dec;5(8):743-9. doi: 10.4161/epi.5.8.13104. Epub 2010 Nov 22.
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An up to date look at lung cancer screening.最新肺癌筛查一览。
Cell Adh Migr. 2010 Jan-Mar;4(1):96-9. doi: 10.4161/cam.4.1.10978. Epub 2010 Jan 18.
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Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.Sox17促进细胞周期进程并抑制TGF-β/Smad3信号传导,以启动呼吸道上皮中的祖细胞行为。
PLoS One. 2009 May 27;4(5):e5711. doi: 10.1371/journal.pone.0005711.
6
Sox17, the canonical Wnt antagonist, is epigenetically inactivated by promoter methylation in human breast cancer.Sox17,经典的 Wnt 拮抗剂,在人类乳腺癌中通过启动子甲基化而被表观遗传失活。
Breast Cancer Res Treat. 2010 Feb;119(3):601-12. doi: 10.1007/s10549-009-0339-8. Epub 2009 Mar 20.
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Different sox17 transcripts during sex differentiation in sea bass, Dicentrarchus labrax.鲈鱼(欧洲鲈,Dicentrarchus labrax)性别分化过程中的不同sox17转录本
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Favorable surgical results for patients with nonsmall cell lung cancer over 80 years old: a multicenter survey.80岁以上非小细胞肺癌患者的良好手术结果:一项多中心调查
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Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer.结直肠癌中经典Wnt拮抗剂含SRY盒基因17的表观遗传失活
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DNA methylation markers and early recurrence in stage I lung cancer.DNA甲基化标志物与I期肺癌的早期复发
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