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长链非编码 RNA GHET1 通过激活 H3K27 乙酰化促进肝癌细胞的肿瘤发生,通过调节 ATF1。

LncRNA GHET1 activated by H3K27 acetylation promotes cell tumorigenesis through regulating ATF1 in hepatocellular carcinoma.

机构信息

Department of Infectious Diseases, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, China.

Department of Infectious Diseases, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, China.

出版信息

Biomed Pharmacother. 2017 Oct;94:326-331. doi: 10.1016/j.biopha.2017.07.046. Epub 2017 Jul 31.

DOI:10.1016/j.biopha.2017.07.046
PMID:28772210
Abstract

BACKGROUND

GHET1 is one of tumor-related lncRNAs. We aimed to explore the functional involvement of GHET1 in hepatocellular carcinoma (HCC).

METHODS

In this study, HCC tissues and the paired normal tissues were collected for the detection of target molecules. The expression level of target molecules in HCC tissues or cell lines was determined by qRT-PCR and western blot, respectively. The expression of endogenous GHET1 and ATF1 was modulated by using cell transfection. RNA pull down assay was performed to examine the interaction between GHET1 and ATF1. ChIP assay was conducted to determine the H3K27Ac acetylation of GHET1 promoter.

RESULTS

H3K27 acetylation activated-GHET1 was upregulated in HCC tissues and cell lines. Moreover, GHET1 silencing could inhibit the proliferation, migration, invasion and EMT of HCC cells in vitro. GHET1 could regulate the expression of ATF1 mRNA and protein; RNA pull-down assays supported that GHET1 could bind to ATF1 protein. Furthermore, overexpression of ATF1 almost completely reversed the GHET1 knockdown mediated inhibition on the proliferation, migration, invasion and EMT of HCC cells.

CONCLUSION

LncRNA GHET1 was intimately involved in the occurrence and development of HCC through regulating ATF1.

摘要

背景

GHE1 是一种与肿瘤相关的 lncRNA。我们旨在探讨 GHE1 在肝细胞癌(HCC)中的功能作用。

方法

本研究收集 HCC 组织及配对的正常组织,检测靶分子。采用 qRT-PCR 和 Western blot 分别检测 HCC 组织或细胞系中靶分子的表达水平。采用细胞转染调节内源性 GHE1 和 ATF1 的表达。采用 RNA 下拉实验检测 GHE1 与 ATF1 之间的相互作用。采用 ChIP 实验检测 GHET1 启动子区 H3K27Ac 乙酰化。

结果

H3K27 乙酰化激活的 GHE1 在 HCC 组织和细胞系中上调。此外,GHE1 沉默可抑制 HCC 细胞在体外的增殖、迁移、侵袭和 EMT。GHE1 可调节 ATF1 mRNA 和蛋白的表达;RNA 下拉实验支持 GHE1 可与 ATF1 蛋白结合。此外,ATF1 的过表达几乎完全逆转了 GHE1 敲低介导的对 HCC 细胞增殖、迁移、侵袭和 EMT 的抑制作用。

结论

lncRNA GHE1 通过调节 ATF1 参与 HCC 的发生和发展。

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