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19q13 KRAB 锌指蛋白 ZFP82 通过抑制 NF-κB 转录和诱导细胞凋亡抑制食管癌细胞的生长和侵袭。

The 19q13 KRAB Zinc-finger protein ZFP82 suppresses the growth and invasion of esophageal carcinoma cells through inhibiting NF-κB transcription and inducing apoptosis.

机构信息

Chongqing Key Laboratory of Molecular Oncology & Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China.

出版信息

Epigenomics. 2019 Jan;11(1):65-80. doi: 10.2217/epi-2018-0092. Epub 2018 Sep 13.

DOI:10.2217/epi-2018-0092
PMID:30211622
Abstract

AIM

To study the epigenetic alternations and biological functions of ZFP82 in esophageal squamous cell carcinoma.

MATERIALS & METHODS: Analysis of ZFP82 expression was carried out by quantitative real-time PCR. Cell function was tested by MTS cell proliferation assay, transwell assay and flow cytometry. Gene mechanisms were studied by reverse transcription-PCR (RT-PCR), quantitative real-time PCR, luciferase reporter assay and Western blot.

RESULTS

ZFP82 promoter methylation was downregulated in esophageal squamous cell carcinoma. ZFP82 ectopic expression suppressed cell function and regulated NF-κB phosphorylation and genes involved in cell cycle arrest and apoptosis. Moreover, ZFP82 methylation was correlated with age, tumor stage and outcome.

CONCLUSION

ZFP82 is a tumor suppressor and is disrupted by promoter CpG methylation during esophageal carcinogenesis.

摘要

目的

研究 ZFP82 在食管鳞癌中的表观遗传学改变和生物学功能。

材料与方法

通过实时定量 PCR 分析 ZFP82 的表达。通过 MTS 细胞增殖试验、Transwell 试验和流式细胞术检测细胞功能。通过逆转录-PCR(RT-PCR)、实时定量 PCR、荧光素酶报告基因检测和 Western blot 研究基因机制。

结果

食管鳞癌中 ZFP82 启动子甲基化下调。ZFP82 异位表达抑制细胞功能,并调节 NF-κB 磷酸化以及参与细胞周期阻滞和凋亡的基因。此外,ZFP82 甲基化与年龄、肿瘤分期和预后相关。

结论

ZFP82 是一种肿瘤抑制因子,在食管癌变过程中被启动子 CpG 甲基化所破坏。

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