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结肠癌中的启动子和组蛋白甲基化以及p16（INK4A）基因表达

Promoter and histone methylation and p16(INK4A) gene expression in colon cancer.

作者信息

Yoruker Ebru Esin, Mert Ufuk, Bugra Dursun, Yamaner Sumer, Dalay Nejat

机构信息

Department of Basic Oncology, Oncology Institute and.

出版信息

Exp Ther Med. 2012 Nov;4(5):865-870. doi: 10.3892/etm.2012.683. Epub 2012 Aug 24.

DOI:10.3892/etm.2012.683
PMID:23226740
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3493785/
Abstract

The inactivation of the cyclin-dependent kinase inhibitor p16(INK4A) gene by hypermethylation is observed in numerous types of cancer. New findings indicate that DNA and histone methylation act in concert in gene silencing. In this study, we investigated the methylation status of the p16(INK4A) gene promoter and the histone 3 lysine 9 residue in the tumors and matched normal tissue samples from patients with colorectal cancer and analyzed their association with gene expression. The methylation and expression of the p16(INK4A) gene were analyzed by real-time PCR, and histone methylation was analyzed by chromatin immunoprecipitation followed by real-time PCR. p16(INK4A) expression was significantly higher in the tumors compared to normal tissue. Mono-, di- and trimethylation levels of the H3K9 residue were similar in the tumor and normal tissue samples. We did not observe any significant correlation between p16(INK4A) methylation or expression and clinical parameters. Our results suggest that epigenetic modifications of the p16(INK4A) gene and histone lysine methylation do not play a major role in colon carcinogenesis.

摘要

在多种癌症中均观察到细胞周期蛋白依赖性激酶抑制剂p16(INK4A)基因因高甲基化而失活。新的研究结果表明，DNA甲基化和组蛋白甲基化在基因沉默过程中协同发挥作用。在本研究中，我们调查了结直肠癌患者肿瘤组织及配对正常组织样本中p16(INK4A)基因启动子的甲基化状态以及组蛋白3赖氨酸9残基的甲基化情况，并分析了它们与基因表达的相关性。通过实时PCR分析p16(INK4A)基因的甲基化和表达情况，通过染色质免疫沉淀结合实时PCR分析组蛋白甲基化情况。与正常组织相比，肿瘤组织中p16(INK4A)的表达显著更高。肿瘤组织和正常组织样本中H3K9残基的单甲基化、二甲基化和三甲基化水平相似。我们未观察到p16(INK4A)甲基化或表达与临床参数之间存在任何显著相关性。我们的结果表明，p16(INK4A)基因的表观遗传修饰和组蛋白赖氨酸甲基化在结肠癌发生过程中不发挥主要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/3688bf1c0378/ETM-04-05-0865-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/d7ce29fe7267/ETM-04-05-0865-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/8a6dab6ea0f8/ETM-04-05-0865-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/3688bf1c0378/ETM-04-05-0865-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/d7ce29fe7267/ETM-04-05-0865-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/8a6dab6ea0f8/ETM-04-05-0865-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5644/3493785/3688bf1c0378/ETM-04-05-0865-g02.jpg

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本文引用的文献

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A 115-bp MethyLight assay for detection of p16 (CDKN2A) methylation as a diagnostic biomarker in human tissues.
高脂饮食通过染色质修饰改变成年雄性大鼠肝脏细胞衰老基因p16(INK4a)的表达。
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Integrated analyses of multi-omics reveal global patterns of methylation and hydroxymethylation and screen the tumor suppressive roles of HADHB in colorectal cancer.多组学综合分析揭示了甲基化和羟甲基化的全局模式，并筛选出 HADHB 在结直肠癌中的肿瘤抑制作用。
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Implications of Genetic and Epigenetic Alterations of CDKN2A (p16(INK4a)) in Cancer.CDKN2A（p16（INK4a））的遗传和表观遗传改变在癌症中的意义。
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用于检测人类组织中 p16（CDKN2A）甲基化的 115-bp MethyLight 检测方法作为一种诊断生物标志物。
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P16 methylation is an early event in cervical carcinogenesis.P16 甲基化是宫颈癌发生的早期事件。
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Cancer epigenetics: linking basic biology to clinical medicine.癌症表观遗传学：将基础生物学与临床医学联系起来。
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