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启动子超甲基化介导的人脑肿瘤中 RUNX3 基因下调。

Promoter hypermethylation-mediated down-regulation of RUNX3 gene in human brain tumors.

机构信息

Department of Medical Biology, Ege University Medical Faculty, Bornova, 35100, Izmir, Turkey,

出版信息

Ir J Med Sci. 2014 Jun;183(2):259-64. doi: 10.1007/s11845-013-1001-3. Epub 2013 Aug 11.

DOI:10.1007/s11845-013-1001-3
PMID:23934435
Abstract

BACKGROUND

The Runx family proteins, including RUNX3, are tissue-restricted transcription factors and play role in neuronal development and tumorigenesis. RUNX3 has an important role in glioblastoma (GBM) tumorigenesis because of its promoter hypermethylation.

AIM

We aimed to evaluate the methylation-mediated expression regulation of RUNX3 gene in brain tumors.

PATIENTS AND METHODS

Cases of meningiomas WHO grade III (3), anaplastic astrocytomas (3), diffuse astrocytoma (3), and GBM (12) were recruited into this study. Real-time quantitative PCR was performed for analyses of DNA promoter methylation and analyses of methylation-mediated expression status of RUNX3 gene was performed by real-time quantitative RT-PCR.

RESULTS

There was no significant difference between methylated and unmethylated quantitative ratio of RUNX3 gene promoter region and also no significant difference in relative ratio of RUNX3 gene expression in brain tumor groups. Methylated and unmethylated ratio in anaplastic astrocytoma, diffuse astrocytoma, GBM, meningioma (WHO grade III) and in all groups were; 1.44, 1.09, 1.51, 1.52 and 1.43, respectively. One allele was found methylated necessarily. No methylation was detected in one case of GBM group and one case of anaplastic astrocytoma group. There was no unmethylated promoter in one of the GBM cases. There were significant differences between relative ratio of RUNX3 gene expression and methylated/unmethylated ratio rates for all cases (p = 0.001) and GBM groups (p = 0.041).

CONCLUSION

This study overemphasized the RUNX3 gene importance in brain tumors, due to the existence of at least one methylated allele.

摘要

背景

Runx 家族蛋白,包括 RUNX3,是组织受限的转录因子,在神经元发育和肿瘤发生中发挥作用。由于启动子超甲基化,RUNX3 在胶质母细胞瘤 (GBM) 肿瘤发生中具有重要作用。

目的

我们旨在评估 RUNX3 基因在脑肿瘤中的甲基化介导的表达调控。

患者和方法

本研究纳入了 III 级脑膜瘤(3 例)、间变性星形细胞瘤(3 例)、弥漫性星形细胞瘤(3 例)和 GBM(12 例)患者。采用实时定量 PCR 分析 DNA 启动子甲基化,采用实时定量 RT-PCR 分析 RUNX3 基因的甲基化介导的表达状态。

结果

RUNX3 基因启动子区域的甲基化和未甲基化定量比之间没有显著差异,脑肿瘤组中 RUNX3 基因表达的相对比值也没有显著差异。间变性星形细胞瘤、弥漫性星形细胞瘤、GBM、脑膜瘤(WHO 分级 III)和所有组中甲基化和未甲基化的比率分别为 1.44、1.09、1.51、1.52 和 1.43。一个等位基因必然发生甲基化。GBM 组和间变性星形细胞瘤组各有 1 例未检测到甲基化。GBM 组中有 1 例无未甲基化启动子。所有病例(p=0.001)和 GBM 组(p=0.041)RUNX3 基因表达的相对比值与甲基化/未甲基化比率之间存在显著差异。

结论

本研究强调了 RUNX3 基因在脑肿瘤中的重要性,因为至少存在一个甲基化等位基因。

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本文引用的文献

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RUNX family: Regulation and diversification of roles through interacting proteins.RUNX 家族:通过相互作用蛋白调节和多样化作用。
Int J Cancer. 2013 Mar 15;132(6):1260-71. doi: 10.1002/ijc.27964. Epub 2012 Dec 19.
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Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis.食管、胃和结肠的胃肠道腺癌表现出明显不同的基因组不稳定性和致癌模式。
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DNA methylation analysis of benign and atypical meningiomas: correlation between RUNX3 methylation and WHO grade.良性和非典型脑膜瘤的DNA甲基化分析:RUNX3甲基化与世界卫生组织分级之间的相关性
J Cancer Res Clin Oncol. 2015 Sep;141(9):1593-601. doi: 10.1007/s00432-015-1930-5. Epub 2015 Feb 4.
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The methylation of a panel of genes differentiates low-grade from high-grade gliomas.一组基因的甲基化可区分低级别和高级别胶质瘤。
Tumour Biol. 2015 May;36(5):3831-41. doi: 10.1007/s13277-014-3025-3. Epub 2015 Jan 8.
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Epigenetic regulation in adult stem cells and cancers.成年干细胞和癌症中的表观遗传调控。
Cell Biosci. 2013 Oct 9;3(1):41. doi: 10.1186/2045-3701-3-41.
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RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making.克隆性骨髓疾病中的RUNX1突变:从传统细胞遗传学到新一代测序,一个历经40年的故事。
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Genome profiling of pancreatic adenocarcinoma.胰腺导管腺癌的基因组分析。
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Control of RUNX3 by histone methyltransferases.组蛋白甲基转移酶对 RUNX3 的调控。
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Hypermethylation downregulates Runx3 gene expression and its restoration suppresses gastric epithelial cell growth by inducing p27 and caspase3 in human gastric cancer.高甲基化下调 Runx3 基因表达,其恢复通过诱导人胃癌中 p27 和 caspase3 抑制胃上皮细胞生长。
J Gastroenterol Hepatol. 2010 Apr;25(4):823-31. doi: 10.1111/j.1440-1746.2009.06191.x.
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RUNX3 is multifunctional in carcinogenesis of multiple solid tumors.RUNX3 在多种实体瘤的致癌作用中具有多功能性。
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RUNX3 protein is overexpressed in human epithelial ovarian cancer.RUNX3蛋白在人上皮性卵巢癌中过表达。
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Hypoxic silencing of tumor suppressor RUNX3 by histone modification in gastric cancer cells.组蛋白修饰导致胃癌细胞中肿瘤抑制因子RUNX3的缺氧沉默
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